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#deck:Molecular Machines
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#columns:id	Front	Back	Explanation	Machine	Tags
atp-synthase-energy-source	ATP synthase sits in the inner membrane of your mitochondria. Pumps in that membrane push protons to one side. What does ATP synthase use to make ATP?	The flow of protons back across the membrane.	Protons flow back through it like water through a turbine below a dam.	atp-synthase	mm::atp-synthase mm::purpose
atp-synthase-ring-spins	Protons flow back into the mitochondrion through ATP synthase, like water through a mill. What does that flow do to the part of the machine in the membrane?	It spins it: the membrane ring turns like a rotor.	Each proton rides the ring almost a full turn and then leaves on the other side.	atp-synthase	mm::atp-synthase mm::parts
atp-synthase-stalk-changes-sites	The spinning ring turns a stalk that reaches into the head of the machine, where ATP is made. What does the turning stalk do to the catalytic sites in the head?	It forces each site to change shape in turn: take in ADP and phosphate, make ATP, then let it go.	The three sites are always in different states, and the pattern turns with the shaft.	atp-synthase	mm::atp-synthase mm::cycle
atp-synthase-atp-per-turn	The head of ATP synthase has three catalytic sites, and each makes one ATP as the stalk turns past. So one full turn of the rotor makes […] ATP.	The head of ATP synthase has three catalytic sites, and each makes one ATP as the stalk turns past. So one full turn of the rotor makes three ATP.		atp-synthase	mm::atp-synthase mm::numbers
atp-synthase-turn-rate	In a working mitochondrion, the rotor of ATP synthase spins very fast. Roughly how many turns does it make each second?	About 100 turns per second.	At three ATP per turn, that is about 300 ATP per second from one machine. The rate is an estimate, not a direct measurement.	atp-synthase	mm::atp-synthase mm::numbers
atp-synthase-body-weight-per-day	Your body remakes ATP all day, almost all of it in ATP synthase. Roughly how much ATP does a person remake each day?	About their own body weight.	Each ATP is spent and recharged within about a minute, so the cell must remake it again and again.	atp-synthase	mm::atp-synthase mm::purpose
atp-synthase-reverse-mode	ATP synthase can work like a turbine or like a pump. With plenty of ATP but a weak proton gradient, which way does it run, and what does it do?	It runs backward: it spends ATP to pump protons across the membrane.	In mitochondria, a small inhibitor protein blocks this reverse mode.	atp-synthase	mm::atp-synthase mm::cycle
atp-synthase-hand-cranked-synthesis	Researchers took the head of ATP synthase without its membrane part and turned its stalk with magnets. No protons were present. What did this show about how the machine makes ATP?	Turning the shaft alone is enough to make ATP; protons only supply the turning.		atp-synthase	mm::atp-synthase mm::debate
atp-synthase-bedaquiline	Tuberculosis bacteria need their own ATP synthase to live. How does the tuberculosis drug bedaquiline stop it?	It jams the rotor ring, so the motor stalls.	It treats multidrug-resistant tuberculosis. Structures of the drug on the human enzyme guide safer versions.	atp-synthase	mm::atp-synthase mm::purpose
atp-synthase-flagellar-link	The bacterial flagellar motor runs on the same kind of proton gradient as ATP synthase. What does it make from that proton flow instead of ATP?	Rotation: it turns the flow straight into turning, with no ATP in between.	Part of the flagellum's export machine also looks like the ATP synthase head, a hint of a shared ancestor.	atp-synthase	mm::atp-synthase mm::purpose
flagellar-motor-what-it-turns	Many bacteria swim with a few long corkscrew tails. The flagellar motor sits at the base of each tail, built into the cell wall. What does the motor do to the tail?	It spins it, like a rotary engine turning a corkscrew.	Several tails turn together as one bundle and push the cell.	flagellar-motor	mm::flagellar-motor mm::purpose
flagellar-motor-fuel	Unlike most motors in a cell, the flagellar motor burns no ATP. What powers it in E. coli?	Protons that flow into the cell across the inner membrane.	Some bacteria, such as Vibrio, use sodium ions instead of protons.	flagellar-motor	mm::flagellar-motor mm::purpose
flagellar-motor-stators-push	A ring of stators grips the cell wall around the motor's rotor. Each stator lets ions into the cell one at a time. What does that ion flow do to the rotor?	It pushes the rotor round, one small step per ion.	Each ion nudges a small ring in the stator, and that ring nudges the rotor like a gear.	flagellar-motor	mm::flagellar-motor mm::parts
flagellar-motor-why-reverse	A bacterium cannot see food. It swims straight for about a second, then tumbles and picks a new direction at random. Why does its motor need to reverse?	Reversing makes the cell tumble, and tumbling less when things get better steers it toward food.	When the motor reverses, the bundle of tails flies apart, so the cell tumbles in place instead of swimming backward.	flagellar-motor	mm::flagellar-motor mm::purpose
flagellar-motor-signal-reverses	A signal protein carries news from the cell's sensors to the motor. When enough of it binds the rotor, what does the motor do?	It reverses its direction of spin.	The switch is very steep, almost all or nothing. The ions still flow the same way; only the contact with the rotor changes.	flagellar-motor	mm::flagellar-motor mm::cycle
flagellar-motor-coast-distance	At the size of a bacterium, water feels like thick syrup. How far does a swimming cell coast after its motors stop?	Less than the width of an atom.	Drag stops the cell almost at once, so there is no gliding.	flagellar-motor	mm::flagellar-motor mm::numbers
flagellar-motor-protons-per-turn	Each proton that passes through a stator moves the rotor only a tiny step. Roughly how many protons does one full turn of the rotor take?	About a thousand.	The measured value, from Streptococcus, is about 1,240 per turn.	flagellar-motor	mm::flagellar-motor mm::numbers
flagellar-motor-catch-bond	Stator units join and leave the motor all the time, like workers who come and go. What makes more of them stay on the motor?	A higher load: they hold on longer when the motor must push hard.	The stator's anchor to the cell wall grips tighter under force.	flagellar-motor	mm::flagellar-motor mm::cycle
flagellar-motor-zero-load-one-unit	Each extra stator unit adds push to the motor. But when the motor turns with almost no load, how fast does one stator unit spin it compared with many?	Just as fast as many.	Extra units only help when the load is high.	flagellar-motor	mm::flagellar-motor mm::numbers
flagellar-motor-dynein-link	Sperm tails and the cilia in your airways are also called flagella, but no rotary motor turns them. How do they move instead?	Dynein motors inside them slide filaments, so the tail bends.	Bacteria rotate a stiff corkscrew; our own flagella beat by bending.	flagellar-motor	mm::flagellar-motor mm::purpose
kinesin-direction	Kinesin is a motor that carries cargo along microtubule tracks. In a nerve cell it pulls cargo outward, away from the cell body. Toward which end of the microtubule does it walk?	Toward the plus end.	Dynein runs on the same tracks and pulls cargo the other way.	kinesin	mm::kinesin mm::purpose direction transport
kinesin-drift-time	A nerve cell can run about a metre, from your spine to your foot, and its proteins are made near the spine. If those proteins only drifted, roughly how long would the trip take?	About 300 years.	Kinesin motors carry the cargo instead, so fast transport makes the trip in a few days.	kinesin	mm::kinesin mm::numbers diffusion axon scale
kinesin-atp-per-step	Each kinesin step moves the cargo about 8 nm, the length of one building block of the microtubule track. What does each step cost the motor?	One ATP.	The motor splits one ATP for each 8 nm step, so at low load it wastes almost none.	kinesin	mm::kinesin mm::numbers energy step
kinesin-hand-over-hand	Kinesin has two identical heads. Scientists put a dye on just one head and watched it walk. The dye jumped about 17 nm, then stayed still for a step, then jumped again. What does that show about how kinesin walks?	The heads take turns: the rear head swings past the bound head and lands ahead, hand over hand.	Each head moves about twice as far as the cargo, which moves 8 nm per step.	kinesin	mm::kinesin mm::cycle hand-over-hand heads
kinesin-diffusion-search	When ATP binds the front head, a short strand zips onto it and points forward, so the free head lands ahead. But this zipping is no leg muscle. What actually carries the free head to its next site?	Random jiggling by heat (diffusion).	Diffusion does the travel and the zipped strand only sets the direction, like a small forward bias.	kinesin	mm::kinesin mm::cycle diffusion power-stroke
kinesin-steps-per-run	A single kinesin does not walk forever. After a while it lets go of the microtubule. About how many steps does it take before it falls off?	About 100 steps, a run of about 1 micrometre.	One head always holds the track while the other moves, so the motor stays on for many steps.	kinesin	mm::kinesin mm::numbers processivity run-length
kinesin-teams-of-motors	One kinesin lets go after about a micrometre, but a nerve cell can be a metre long. How does the cargo still reach the far end?	Teams of motors grab on again and again.	A cargo bubble carries several motors, so when one lets go, others keep it on the track.	kinesin	mm::kinesin mm::purpose teams axon
kinesin-dynein-tug	Cargo bubbles in a nerve cell carry more than one kind of motor. Kinesin pulls them outward. Which motor on the same tracks pulls the other way, back toward the cell body?	Dynein.	Vesicles from the brain carry a few kinesins and a few dyneins at once.	kinesin	mm::kinesin mm::purpose dynein link
kinesin-nerve-disease	Long nerve cells depend on kinesin to keep their far ends supplied. What kind of illness can a mutation in a nerve kinesin gene cause?	Nerve disease, such as a hereditary spastic paraplegia or ALS.	A mutation in the motor part of the nerve kinesin KIF5A causes one form of hereditary spastic paraplegia, and the same gene is linked to ALS.	kinesin	mm::kinesin mm::purpose disease nerve
kinesin-myosin-shared-core	Kinesin walks on microtubules and myosin walks on actin, and their protein sequences are almost unrelated. What do their motor cores still share?	The same fold, so they probably share a common ancestor.	A switch in the core changes shape between the ADP and ATP states, much like in myosin and in G proteins.	kinesin	mm::kinesin mm::debate evolution myosin link
myosin-track	Myosin is the motor in your muscles, and in other cells it also hauls cargo. Along which kind of filament does it pull?	Actin filaments.	Kinesin and dynein walk on microtubules instead.	myosin	mm::myosin mm::purpose actin track
myosin-lever-swing	A myosin head binds actin and then lets its phosphate go. What does the head do next that pulls the filament along?	It swings its lever arm: the power stroke.	The lever swings through a large angle, mostly along the filament, and its end moves the load.	myosin	mm::myosin mm::cycle power-stroke lever
myosin-atp-frees-head	After the power stroke, the myosin head stays stuck tight to actin with an empty fuel pocket. What must bind to make the head let go?	A new ATP.	A head cannot hold both ATP and actin tightly, so gripping ATP frees it.	myosin	mm::myosin mm::cycle atp release
myosin-recovery-stroke	Once free of actin, the myosin head closes around its ATP and splits it. What does this do to the lever?	It swings the lever back and cocks it for the next stroke.	The head holds ADP and phosphate in this primed state until it binds actin again.	myosin	mm::myosin mm::cycle recovery priming
myosin-uyeda-lever-test	Inside the head only a small part turns, and a long lever arm turns that into a big stroke. When engineers made the lever longer, what happened to the speed of the motor?	It went up, in step with the lever length.	Longer levers give longer strokes, so the filaments glide faster. Shorter levers glide slower.	myosin	mm::myosin mm::parts lever speed
myosin-muscle-layout	Each myosin stroke moves only a few nanometres, yet a muscle shortens by centimetres. How does the layout of muscle add these strokes up?	Myosins sit side by side, so their forces add; sarcomeres sit end to end, so their shortenings add.	Like train carriages, units in a row add their travel, and units side by side add their force.	myosin	mm::myosin mm::purpose muscle sarcomere
myosin-gain-to-hand	A myosin stroke starts with a movement of about half a nanometre near one phosphate in the head. By the time it reaches your hand, roughly how many times larger has that movement grown?	About 30 million times.	The head's lever, the heads taking turns, thousands of sarcomeres in a row and the lever of the arm each multiply it.	myosin	mm::myosin mm::numbers scale gain
myosin-muscle-low-duty	Muscle myosin heads let go of actin for most of their cycle, and each head works on its own clock. How does muscle still pull steadily?	Many heads work together, so at any moment some are pulling.	It is like a rowing crew, except the rowers do not pull in time.	myosin	mm::myosin mm::cycle ensemble duty-ratio
myosin-cardiac-drugs	Cardiac myosin drives every heartbeat, and it is now a drug target. What do the new cardiac myosin drugs do to this motor?	One turns the motor up and one turns it down.	The activator and the inhibitor bind the same pocket in the head. Regulators have approved the inhibitor, mavacamten.	myosin	mm::myosin mm::purpose drugs heart
myosin-link-serca	A calcium signal switches muscle myosin on. Which machine switches it off again, and how?	SERCA, by pumping the calcium away.		myosin	mm::myosin mm::purpose serca link calcium
dynein-direction	Kinesin carries cargo outward along microtubules. Cytoplasmic dynein runs on the same tracks. Which way does dynein carry its cargo?	Toward the minus end, back toward the centre of the cell.	So kinesin and dynein pull cargo in opposite directions, and nerve vesicles carry both.	dynein	mm::dynein mm::purpose direction transport
dynein-mucus-escalator	Every breath brings in dust and germs. Dynein motors drive the tiny hairs, called cilia, that line your airways. What do these cilia move?	A sheet of mucus, up toward your throat.	The mucus traps dust and germs and moves a few millimetres a minute.	dynein	mm::dynein mm::purpose cilia lungs
dynein-lung-cilia-count	The cilia in your airways each beat 10 to 20 times a second, all day. Roughly how many motile cilia line an adult lung?	About three trillion.		dynein	mm::dynein mm::numbers cilia scale
dynein-sliding-to-bending	Inside a cilium, dynein arms pull one rail past the next. The rails are tied together, so they cannot slide far. What does the cilium do instead?	It bends.	Like a bimetal strip, two tied layers turn a change in length into a bend. In a cilium, motors make that change.	dynein	mm::dynein mm::cycle cilia bending
dynein-pcd	In a rare disease, the airway cilia are missing their dynein arms. What goes wrong in the lungs?	The cilia cannot beat, so the mucus does not clear.	This is primary ciliary dyskinesia. In about half of the people affected, the organs also develop on the wrong side.	dynein	mm::dynein mm::purpose disease cilia
dynein-atp-closes-ring	Each dynein motor head is a ring of six ATP-binding units, with a long stalk that ends in a small foot on the track. What happens to the ring when ATP binds?	It closes.	The closing slides the stalk helices, and the foot at the tip lets go of the microtubule.	dynein	mm::dynein mm::cycle ring atp
dynein-linker-springs-back	The closed ring forces dynein's lever-like linker into a bent shape. The head then lands on the track again and its phosphate leaves. What does the linker do, and what moves?	It straightens, and the tail and cargo move forward: the power stroke.	The foot holds the track while the bent linker springs back.	dynein	mm::dynein mm::cycle linker power-stroke
dynein-activators	On its own, human cytoplasmic dynein is mostly switched off. What does it need before it carries cargo?	Partner proteins: dynactin and a cargo adaptor, which also link it to the cargo.		dynein	mm::dynein mm::parts activation partners
dynein-tug-of-war	Kinesin and dynein pull the same cargo in opposite directions. In a test tube, one dynein complex was tied to one kinesin. What happened?	They held each other back, and the pair crawled slowly.	The dynein complex resisted the kinesin. Mixed teams like this could give controlled two-way transport.	dynein	mm::dynein mm::debate kinesin tug-of-war
dynein-cell-division	Cytoplasmic dynein is not only a cargo carrier. When a cell divides, what does dynein help to do?	Build and place the spindle and move the chromosomes.	It also helps separate the centrosomes and silence the checkpoint.	dynein	mm::dynein mm::purpose cell-division spindle
ribosome-purpose	Every protein in your body, and every machine in this atlas, comes off one kind of machine. What does the ribosome do?	It reads a messenger RNA and builds the matching protein chain.	RNA polymerase writes the messenger RNA. The ribosome reads it.	ribosome	mm::ribosome mm::purpose
ribosome-three-letters	The ribosome reads a messenger RNA like a tape. It adds one amino acid for every […] letters it reads.	The ribosome reads a messenger RNA like a tape. It adds one amino acid for every three letters it reads.	Each three-letter word is a codon. A matching tRNA brings the amino acid for it.	ribosome	mm::ribosome mm::cycle
ribosome-check	A tRNA arrives at the ribosome with an amino acid, and the ribosome tests it against the codon. What happens to a tRNA that does not match?	It falls off again and is rejected.	Wrong tRNAs bind fast and fall off fast, so the ribosome can try many at little cost.	ribosome	mm::ribosome mm::cycle
ribosome-rna-joins	The ribosome is built from RNA and protein. At its core two amino acids are joined into a chain. Which of the two materials does that chemistry?	RNA: no protein sits near the new bond.	So the ribosome is an RNA machine at its heart. Its proteins sit on the surface.	ribosome	mm::ribosome mm::parts
ribosome-ratchet	After each bond forms, the ribosome must move on to the next codon. How do its two subunits move to make that step?	They rotate against each other, and the mRNA moves on by one codon.	The first part of the turn happens by thermal motion. A helper protein with GTP then completes the step.	ribosome	mm::ribosome mm::cycle
ribosome-fuel	The ribosome uses helper proteins to bring each tRNA and to move along the mRNA. What fuel do these helpers burn?	GTP.	The cell recharges GTP with a phosphate taken from ATP.	ribosome	mm::ribosome mm::purpose
ribosome-mammal-rate	A ribosome adds amino acids to the chain one at a time. In mammal cells, roughly how many does it add each second?	About five or six.	At that speed a typical protein of 400 amino acids takes a little over a minute.	ribosome	mm::ribosome mm::numbers
ribosome-body-protein	Your body builds protein all day, to grow, to repair and to replace what wears out. Roughly how much protein does it build each day?	A few hundred grams.	Every gram of it comes off ribosomes.	ribosome	mm::ribosome mm::numbers
ribosome-antibiotics	Many antibiotics kill bacteria by jamming their ribosomes. How do these drugs stop the machine?	Each drug binds one site on the ribosome's RNA, for example in the exit tunnel or the catalytic centre.	Structures show where each drug class sits, which helps people design new drugs.	ribosome	mm::ribosome mm::parts
ribosome-rna-first	The catalytic centre of the ribosome holds no protein. The proteins only sit on the surface and hold the RNA folds stable. What does that hint about how the ribosome first evolved?	RNA came first, and protein was added around it.	This fits an RNA-first origin.	ribosome	mm::ribosome mm::debate
rna-polymerase-makes-mrna	To use a gene, the cell first copies it. RNA polymerase II copies a DNA gene into […], the molecule that ribosomes read.	To use a gene, the cell first copies it. RNA polymerase II copies a DNA gene into messenger RNA, the molecule that ribosomes read.	The DNA stays in the nucleus. Only the copy goes out to the ribosomes.	rna-polymerase	mm::rna-polymerase mm::purpose
rna-polymerase-same-genome-different-cells	A skin cell and a nerve cell carry the same full genome. What makes them different, in terms of what RNA polymerase II does?	They copy different genes.	Like a scribe in a huge library, the cell copies only the pages it needs.	rna-polymerase	mm::rna-polymerase mm::purpose
rna-polymerase-opens-dna	The letters RNA polymerase II must read are hidden inside the DNA double helix. What does it do to the DNA first?	It clamps onto it and opens a short bubble, about one turn.	It then pairs RNA letters with one of the two DNA strands. Cas9 also opens DNA and reads one strand.	rna-polymerase	mm::rna-polymerase mm::cycle
rna-polymerase-energy-source	Many machines burn ATP as a separate fuel. What pays for each letter that RNA polymerase II adds to the RNA?	The incoming building block itself: the energy in its triphosphate.	Each new letter arrives as a triphosphate. The release of pyrophosphate drives the chain forward.	rna-polymerase	mm::rna-polymerase mm::purpose
rna-polymerase-brownian-ratchet	After each new letter, the polymerase must move one step along the DNA. How does it move forward?	It jiggles back and forth by thermal motion, and the next incoming building block catches it in the forward position.	This is called a Brownian ratchet. Force data fit it better than a power stroke.	rna-polymerase	mm::rna-polymerase mm::debate
rna-polymerase-proofreading-backtrack	Now and then a wrong letter slips into the new RNA. How does the polymerase fix it?	It backs up one step and cuts off the RNA end that holds the error.	The same active site that adds letters also cuts the wrong one off.	rna-polymerase	mm::rna-polymerase mm::cycle
rna-polymerase-error-rate	Even with proofreading, RNA polymerase II sometimes makes a mistake. Roughly how many mistakes does it make per million letters?	About four.	This was measured across all the messenger RNAs of a worm.	rna-polymerase	mm::rna-polymerase mm::numbers
rna-polymerase-letters-per-second	RNA polymerase II writes RNA one letter at a time. Roughly how many letters does it add each second in human cells?	About 25 to 60.	That is a few thousand letters a minute.	rna-polymerase	mm::rna-polymerase mm::numbers
rna-polymerase-dystrophin-time	Short genes take minutes to copy. Roughly how long does one polymerase take to copy the longest human gene, dystrophin?	Most of a day: about 16 hours.	Dystrophin is over two million letters long.	rna-polymerase	mm::rna-polymerase mm::numbers
rna-polymerase-toxins	Some toxins and antibiotics kill by stopping RNA polymerase. How do they stop it?	They jam the moving parts next to the active site, so the enzyme slows or stops.	The toxin alpha-amanitin binds next to the bridge helix. Other drugs hold the trigger loop away from the new letter.	rna-polymerase	mm::rna-polymerase mm::parts
groel-what-it-does	A new protein chain can get stuck half-folded, and its sticky patches can clump with other chains. What does GroEL do with such a chain?	It shuts the chain in a sealed chamber, where it folds alone.	A lid protein, GroES, closes the chamber over one ring. Inside, the chain cannot meet other chains, so it cannot clump.	groel	mm::groel mm::purpose folding aggregation
groel-fuel	GroEL closes and opens its lid again and again, once per folding round. What fuel pays for each round?	ATP.	One ring binds and splits seven ATP in each cycle. ATP synthase makes the ATP that GroEL spends.	groel	mm::groel mm::purpose energy atp
groel-capture-hydrophobic	The rim of an open GroEL ring is water-repelling and sticky. A folded protein hides its own water-repelling parts. What lets the rim catch an unfolded protein?	The unfolded protein still shows water-repelling stretches, and the rim binds them.	A folded protein buries these stretches inside, so the rim ignores it.	groel	mm::groel mm::cycle capture hydrophobic
groel-why-no-aggregation-inside	Once the lid is on, the GroEL chamber has water-loving walls and room for just one protein. Why can the protein not clump in there?	It meets no other chains, so it has nothing to stick to.	The walls are not sticky either, so the chain is free to fold.	groel	mm::groel mm::cycle folding chamber
groel-hydrolysis-timer	With the lid on, GroEL splits its ATP slowly. After the split, the ring holds the lid less tightly. So what does the time to split ATP control?	How long the chamber stays shut.	The ATP split works as a timer that gives the protein time to fold before the lid can come off.	groel	mm::groel mm::cycle atp timer
groel-what-opens-old-chamber	GroEL has two rings that take turns, so only one chamber folds a protein at a time. What makes the closed chamber on one ring open again?	ATP and a new protein binding the other ring.	That binding throws off the lid and the protein from the first ring. The protein leaves whether it has folded or not.	groel	mm::groel mm::cycle rings alternation
groel-sr1-folds-inside	Scientists built a GroEL with a single ring that closes its lid but never opens again. A protein trapped inside still became active. What does this show?	The protein folds inside the closed chamber, not only after it leaves.	It is open how much the chamber actively helps the fold, beyond keeping other chains away. Some proteins fold faster in a slightly smaller chamber.	groel	mm::groel mm::debate chamber folding
groel-share-of-proteins	GroEL is a busy helper in a growing E. coli cell, and it gets busier under heat stress. Roughly what share of the cell's cytoplasmic proteins pass through it in normal growth?	About one in ten.	Measured in living cells as 10 to 15 percent, and 30 percent or more under heat stress.	groel	mm::groel mm::numbers scale
groel-essential-for-growth	Most E. coli proteins fold without help, but a small group of hard cases need GroEL. What happens to E. coli that has no GroEL?	It cannot grow at all.	About 85 proteins need GroEL to fold, and some of those are essential for life.	groel	mm::groel mm::purpose essential
groel-proteasome-chamber	GroEL and the proteasome are both closed chambers that hold one protein. What is the difference in what happens to the protein inside each?	In GroEL it gets a place to fold; in the proteasome it gets destroyed.	In your cells, many new proteins that fold wrong go to the proteasome.	groel	mm::groel mm::purpose links proteasome
proteasome-what-it-does	Your body breaks down and rebuilds about 300 to 400 grams of its own protein every day. Most of that breakdown happens in the proteasome. What does the proteasome do to a protein it takes in?	It pulls the protein straight and cuts it into short pieces.	The pieces become building blocks for new proteins.	proteasome	mm::proteasome mm::purpose destruction turnover
proteasome-tag-signal	A cell must pick out the few proteins it wants gone among thousands of others. What mark does it put on a protein to send it to the proteasome?	A chain of the small protein ubiquitin.	The tag lets the proteasome pick out one protein among thousands. The proteasome strips the tag off as it pulls the protein in.	proteasome	mm::proteasome mm::purpose ubiquitin tag
proteasome-fuel	A ring of six motor parts sits on top of the proteasome's cutting barrel. They grip the tagged protein and pull it in. What fuel do these motors burn?	ATP.	Each motor part splits ATP, and they fire in a set order around the ring.	proteasome	mm::proteasome mm::parts energy motor
proteasome-staircase-one-way	The six motor parts of the proteasome stand in a spiral staircase around the protein chain. Why does the chain move one way only?	The motors split ATP in order around the ring, so each grips the chain in turn, hand over hand.	The motor at the bottom lets go and climbs to the top. Blocking ATP binding in one motor cuts the ring's ATP use by about two thirds.	proteasome	mm::proteasome mm::cycle motor staircase
proteasome-sealed-barrel-why	The proteasome's cutting sites sit inside a sealed barrel, behind a gate that the motor opens. Why does the cell hide them there?	So only a chain fed through the gate meets them, and the cell's other proteins stay safe.	Like a paper shredder with a doorman: only tagged proteins get in, and the blades are enclosed.	proteasome	mm::proteasome mm::purpose barrel safety
proteasome-atp-cost	Pulling a folded protein apart costs energy, and tighter folds cost more. Roughly how many ATP does the proteasome spend to destroy one tagged test protein?	Dozens: about 50 to 80.	It takes about 13 seconds per protein. ATP synthase makes the ATP the proteasome spends.	proteasome	mm::proteasome mm::numbers energy cost
proteasome-vs-ribosome-rate	Ribosomes build proteins and proteasomes destroy them, and together they set protein levels. In one mouse cell line, how does the destroying rate compare with the building rate?	The proteasomes destroy about half as many proteins per minute as the ribosomes make.	The amino acids from destroyed proteins feed the ribosomes again.	proteasome	mm::proteasome mm::numbers links ribosome
proteasome-pieces-fate	Most of the short pieces the proteasome makes are recycled into new proteins. What happens to a few of them?	They go on display at the cell surface, where the immune system checks them.	They are a sample of what the cell is making.	proteasome	mm::proteasome mm::purpose immune
proteasome-drug-myeloma	The proteasome is also a drug target. The drug bortezomib blocks it. Which disease was this drug approved to treat?	Multiple myeloma, a blood cancer.	It was the first proteasome drug approved in the US.	proteasome	mm::proteasome mm::purpose medicine drug
proteasome-protac	Drug designers now want the proteasome to destroy a protein of their own choice. How does a PROTAC molecule make that happen?	It ties the chosen protein to the enzyme that adds the ubiquitin tag, so the protein gets marked for destruction.	Related tools, such as degradation tags, can remove a chosen protein within minutes.	proteasome	mm::proteasome mm::debate medicine design
serca-job	A muscle contracts when calcium floods out of a store inside each fibre. What job does SERCA do after each contraction?	It pumps the calcium back into the store, so the muscle relaxes.	The store is the sarcoplasmic reticulum, a membrane sleeve around every muscle fibre. SERCA sits in its membrane.	serca	mm::serca mm::purpose
serca-ca-per-atp	SERCA pays for its work with ATP: each ATP it spends pushes […] calcium ions into the store.	SERCA pays for its work with ATP: each ATP it spends pushes two calcium ions into the store.		serca	mm::serca mm::numbers
serca-gradient-size	SERCA pushes calcium uphill, into a store that already holds a lot. Roughly how much more free calcium is inside the store than in the resting muscle fibre?	About 4,000 times more.	One ATP gives enough energy to push two calcium ions up this gradient.	serca	mm::serca mm::numbers
serca-airlock-doors	SERCA works like an airlock: one door opens to the fibre, it shuts, then a door opens to the store. Why must the two doors never be open at the same time?	So the calcium cannot leak back out of the store.	Unlike an airlock, SERCA's doors are driven by the energy of ATP.	serca	mm::serca mm::cycle
serca-phosphorylates-itself	SERCA does not simply burn ATP like fuel in an engine. What does it do with the phosphate group of the ATP?	It puts the phosphate on itself, and that drives its change of shape.	The shape change closes the door to the fibre and opens the way to the store. Later the pump removes the phosphate and resets.	serca	mm::serca mm::cycle
serca-protons-empty-sites	After SERCA lets its two calcium ions go inside the store, its binding sites are empty. What fills the empty seats for the trip back?	Protons, which move the other way.		serca	mm::serca mm::cycle
serca-resting-oxygen	Even at rest, a muscle keeps its pumps busy to hold calcium in the store. About how much of resting muscle's oxygen use goes to SERCA?	Close to half.	Measured at 40 to 50 percent in resting mouse muscle.	serca	mm::serca mm::numbers
serca-thapsigargin-tool	A plant toxin, thapsigargin, jams SERCA. Why did it become a standard lab tool for studying calcium?	It blocks SERCA at a tiny dose and leaves other calcium pumps and channels alone.		serca	mm::serca mm::debate
serca-heart-failure-gene-transfer	In heart failure, the heart's calcium cycling falls, and SERCA activity falls with it. What treatment idea tries to fix this, and how well has it worked?	Adding more SERCA by gene transfer; it helped failing heart muscle, but results in patients have been mixed.		serca	mm::serca mm::debate
serca-myosin-link	Calcium switches on myosin, the motor that makes muscle contract. How does SERCA switch myosin off at the end of a contraction?	It takes the calcium away.	SERCA also spends the ATP that ATP synthase makes, running the opposite trade: ATP in, ion gradient out.	serca	mm::serca mm::purpose
hemoglobin-job	Every cell needs oxygen to make ATP, but water carries very little oxygen. So blood packs it into hemoglobin. What does hemoglobin carry, and from where to where?	Oxygen, from the lungs to the tissues.	It grabs oxygen in the lungs and lets go in the tissues. It carries about 98.5 percent of the oxygen in blood.	hemoglobin	mm::hemoglobin mm::purpose oxygen transport
hemoglobin-no-fuel	Most machines in the atlas burn ATP or ride an ion flow. Hemoglobin spends no chemical fuel at all. What does the work of loading and unloading oxygen instead?	The oxygen gradient and the molecule's own shape switch.	Where oxygen is high it fills up; where oxygen is low it lets go.	hemoglobin	mm::hemoglobin mm::purpose energy no-fuel
hemoglobin-sigmoid-why	Hemoglobin has four oxygen seats, one on each heme. It fills up fully in the lungs and empties well in the tissues. How do the four seats work to make this possible?	As a team: the whole molecule flips from a weak-grip shape to a strong-grip shape.	Once some seats fill, the rest fill more easily. This makes the loading curve S-shaped.	hemoglobin	mm::hemoglobin mm::cycle cooperativity switch
hemoglobin-iron-into-plane	Without oxygen, the iron in each heme sits a little out of its flat ring. What happens when the first oxygen binds that iron?	The iron moves into the ring and pulls a helix of the protein with it.	This turns a tiny move of the iron into a move of a whole helix. The shift travels to the contact between the two halves and tips the switch.	hemoglobin	mm::hemoglobin mm::cycle iron heme
hemoglobin-acid-releases-oxygen	Working muscle makes acid and carbon dioxide. Hemoglobin is like a sponge that squeezes itself in acid. What do acid and carbon dioxide do to hemoglobin there?	They push it back to its weak-grip shape, so it lets go of more oxygen.	They bind the weak-grip shape better than the strong-grip one. 2,3-BPG in the red cell works the same way.	hemoglobin	mm::hemoglobin mm::cycle bohr release
hemoglobin-per-red-cell	A red blood cell is a tiny bag packed with hemoglobin, and your body has about 25 trillion of them. Roughly how many hemoglobin molecules does one red cell hold?	About 270 million.	With four oxygen seats each, one full red cell carries about a billion oxygen molecules.	hemoglobin	mm::hemoglobin mm::numbers scale
hemoglobin-rbc-no-burn	A red blood cell carries about a billion oxygen molecules on each trip. Why does it not burn that oxygen itself?	It has no mitochondria.	A mature red cell has no nucleus and no mitochondria, so it delivers the oxygen instead of using it.	hemoglobin	mm::hemoglobin mm::purpose red-cell
hemoglobin-cas9-fetal	Fetal hemoglobin grips oxygen more tightly than adult hemoglobin, so a fetus can take oxygen from its mother's blood. How does an approved Cas9 therapy use this to treat sickle cell disease?	It edits a person's blood stem cells so their red cells make fetal hemoglobin again.	Turning the fetal form back on treats sickle cell disease and beta-thalassaemia, without changing the hemoglobin protein itself.	hemoglobin	mm::hemoglobin mm::purpose disease cas9
hemoglobin-myoglobin-no-switch	Myoglobin in muscle has the same fold as one hemoglobin chain, but it is a single chain with a single heme. Why can it not switch as a team like hemoglobin?	It has no partner chains, so there is no contact that can pass the signal on.	Teamwork needed a stable contact between chains, where a change in one chain could become a change of the whole molecule.	hemoglobin	mm::hemoglobin mm::parts evolution myoglobin
hemoglobin-beyond-two-states	The classic picture says hemoglobin has just two shapes, a weak-grip one and a strong-grip one. What does newer work add to that picture?	Smaller changes inside each shape also change the grip, so two shapes are not the whole story.	Effectors can lower oxygen grip even while the molecule stays in its strong-grip shape.	hemoglobin	mm::hemoglobin mm::debate allostery open-question
cas9-job	Viruses attack bacteria all the time, and many bacteria fight back with a memory. What does Cas9 do for the bacterium that carries it?	It finds the invader's DNA and cuts it.		cas9	mm::cas9 mm::purpose
cas9-memory	When a bacterium survives a virus attack, it keeps a record of the invader in its own genome. What does it save?	A short piece of the virus's DNA, which its daughters inherit.	The cell copies each saved piece into a guide RNA, and each guide loads into one Cas9.	cas9	mm::cas9 mm::purpose
cas9-address-in-rna	Cas9 is one protein, but it can be aimed at almost any DNA sequence. Where does it carry the address of its target?	In its guide RNA, not in the protein.	A new guide gives a new target. In the ribosome too, RNA carries the information.	cas9	mm::cas9 mm::parts
cas9-pam-search	Cas9 cannot see a matching sequence from afar. What does it check at each spot as it moves along the DNA?	A short tag next to the target, the PAM. It opens the DNA only where one fits.	Reading this short tag first lets Cas9 skip most of the genome quickly.	cas9	mm::cas9 mm::cycle
cas9-zipper	At a PAM, the guide pairs with the DNA one letter at a time, like a zipper. What happens when a wrong letter turns up early, next to the PAM?	The zipper stops and the DNA is spared.		cas9	mm::cas9 mm::cycle
cas9-double-cut	When all 20 letters of the guide match the DNA, Cas9 brings in its two cutting blades. What does it do to the DNA?	It cuts both strands, so the DNA breaks right through.	Each blade cuts one strand, and the two fire together.	cas9	mm::cas9 mm::cycle
cas9-no-fuel	Many machines in this atlas burn ATP. What powers Cas9 as it opens DNA and decides to cut?	No fuel: Cas9 spends no ATP. Base pairing between guide and DNA pays for its switch.	Cutting also needs magnesium ions.	cas9	mm::cas9 mm::purpose
cas9-search-time	Cas9 checks spot after spot across a whole genome. Roughly how long does one Cas9 take to find its target in a bacterium?	About six hours.	So a cell keeps many copies of Cas9.	cas9	mm::cas9 mm::numbers
cas9-cut-decision	Cas9 can stay bound to DNA that only partly matches its guide. So what makes the final call on whether it cuts?	A shape change: one cutting blade must swing into its active place, and it does so only on a full match.	Binding is far less choosy than cutting. High-fidelity versions of Cas9 tune this switch.	cas9	mm::cas9 mm::debate
cas9-therapy-disease	People now use Cas9 to edit genes in patients. Which disease did the first approved Cas9 therapy treat?	Sickle cell disease (and transfusion-dependent beta-thalassaemia).	Cas9 edits the patient's own blood stem cells, so their red cells make fetal hemoglobin.	cas9	mm::cas9 mm::purpose
shared-rotary-ion-motors	Kinesin, dynein and myosin walk along tracks. Two other machines in the atlas spin like wheels instead, driven by ions that flow across a membrane. Which two are these rotary motors?	ATP synthase and the bacterial flagellar motor.	ATP synthase makes most of the cell's ATP. The flagellar motor turns a stiff corkscrew from its base.	shared	mm::shared mm::parts rotary ion-gradient
shared-flagellum-skips-atp	ATP synthase and the flagellar motor both run on a flow of protons into the cell. ATP synthase turns that flow into ATP. What does the flagellar motor do differently with the same energy?	It turns the proton flow straight into rotation, with no ATP in between.	Some bacteria drive their flagellar motor with sodium ions instead of protons.	shared	mm::shared mm::cycle rotary energy
shared-no-fuel-machines	Most machines in the atlas burn ATP or GTP, or ride an ion flow across a membrane. Two of them spend no chemical fuel at all. Which two?	Cas9 and hemoglobin.	Base pairing between RNA and DNA powers the switch in Cas9. The oxygen gradient and a shape switch do the work in hemoglobin.	shared	mm::shared mm::purpose energy no-fuel
shared-ribosome-gtp	Most motors in the atlas burn ATP. The ribosome's helpers burn a close cousin of ATP instead, which the cell recharges from ATP. Which fuel is it?	GTP.	An enzyme moves a phosphate from ATP to recharge the GTP, so the ribosome still depends on ATP synthase.	shared	mm::shared mm::purpose energy gtp
shared-serca-reverse-trade	ATP synthase uses an ion gradient across a membrane to make ATP. SERCA, the calcium pump in muscle, does the opposite trade. What is that trade?	It spends ATP to build an ion gradient: it pumps calcium out of the cytoplasm.	Taking the calcium away is what switches muscle myosin off.	shared	mm::shared mm::purpose energy pump
shared-same-tracks-opposite	Kinesin and dynein both walk on microtubule tracks, and vesicles in nerve fibres carry both motors. How do their jobs differ?	They pull cargo in opposite directions along the same tracks.	Kinesin walks toward the plus end of a microtubule, dynein toward the minus end.	shared	mm::shared mm::cycle walking transport
shared-kinesin-myosin-cousins	Kinesin and myosin are cousins: they share the same catalytic core that burns ATP. Each walks on a different kind of track. Which tracks?	Kinesin walks on microtubules; myosin walks on actin.	Dynein also pulls with a lever-like part, but it belongs to an unrelated motor family.	shared	mm::shared mm::parts walking evolution
shared-six-unit-rings	Dynein and the proteasome are very different machines, but both are built around a ring of six units that burn ATP. What does each ring move?	Dynein's ring walks the motor along a microtubule; the proteasome's ring pulls a protein chain into its cutting barrel.	In both, the ATP-burning units belong to the same large family of ring-shaped motors.	shared	mm::shared mm::parts rings atpase
shared-rna-guided	Cas9 and the ribosome are the two machines in the atlas where RNA carries the information. What does the chemistry in each one?	In the ribosome, RNA itself joins the amino acids; in Cas9, protein does the cutting.	Cas9 compares DNA with its RNA guide and cuts; the ribosome reads messenger RNA and builds a protein.	shared	mm::shared mm::parts rna catalysis
shared-atp-body-weight	Kinesin, myosin, SERCA, GroEL and the proteasome all spend ATP, and most of it comes from ATP synthase. Roughly how much ATP does a human body remake each day?	About its own body weight.	This is an upper estimate from oxygen use: about 54 to 68 kg a day for a college student.	shared	mm::shared mm::numbers energy scale