{"format":"molecular-machines.cards","version":1,"updated":"2026-10-12","decks":[{"machine":"proteasome","name":"Proteasome","count":10,"url":"/learn/cards/proteasome.json"}],"cards":[{"id":"proteasome-what-it-does","machine":"proteasome","kind":"qa","prompt":"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?","answer":"It pulls the protein straight and cuts it into short pieces.","explanation":"The pieces become building blocks for new proteins.","section":"summary","topic":"purpose","sources":["machine:summary","story:summary","fact:P1"],"tags":["destruction","turnover"],"difficulty":1,"url":"/machines/proteasome#summary","cites":[{"source":"machine:summary","machine":"proteasome","label":"Summary","section":"summary"},{"source":"story:summary","machine":"proteasome","label":"Big picture","section":"story"},{"source":"fact:P1","machine":"proteasome","label":"Protein broken down and rebuilt per day: 300–400 g per day","section":"story"}]},{"id":"proteasome-tag-signal","machine":"proteasome","kind":"qa","prompt":"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?","answer":"A chain of the small protein ubiquitin.","explanation":"The tag lets the proteasome pick out one protein among thousands. The proteasome strips the tag off as it pulls the protein in.","section":"summary","topic":"purpose","sources":["machine:summary","step:A tagged protein arrives","stop:tag","mechanism:Deubiquitination"],"tags":["ubiquitin","tag"],"difficulty":1,"url":"/machines/proteasome#summary","cites":[{"source":"machine:summary","machine":"proteasome","label":"Summary","section":"summary"},{"source":"step:A tagged protein arrives","machine":"proteasome","label":"Step: A tagged protein arrives","section":"mechanism"},{"source":"stop:tag","machine":"proteasome","label":"Big picture: The tag","section":"story"},{"source":"mechanism:Deubiquitination","machine":"proteasome","label":"Step: Deubiquitination","section":"mechanism"}]},{"id":"proteasome-fuel","machine":"proteasome","kind":"qa","prompt":"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?","answer":"ATP.","explanation":"Each motor part splits ATP, and they fire in a set order around the ring.","section":"summary","topic":"parts","sources":["machine:energy","stat:ATPase subunits","mechanism:Translocation in steps"],"tags":["energy","motor"],"difficulty":1,"url":"/machines/proteasome#summary","cites":[{"source":"machine:energy","machine":"proteasome","label":"Summary","section":"summary"},{"source":"stat:ATPase subunits","machine":"proteasome","label":"Key number: ATPase subunits","section":"summary"},{"source":"mechanism:Translocation in steps","machine":"proteasome","label":"Step: Translocation in steps","section":"mechanism"}]},{"id":"proteasome-staircase-one-way","machine":"proteasome","kind":"qa","prompt":"The six motor parts of the proteasome stand in a spiral staircase around the protein chain. Why does the chain move one way only?","answer":"The motors split ATP in order around the ring, so each grips the chain in turn, hand over hand.","explanation":"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.","section":"mechanism","topic":"cycle","sources":["mechanism:Translocation in steps","step:Hand over hand"],"tags":["motor","staircase"],"difficulty":2,"url":"/machines/proteasome#mechanism","cites":[{"source":"mechanism:Translocation in steps","machine":"proteasome","label":"Step: Translocation in steps","section":"mechanism"},{"source":"step:Hand over hand","machine":"proteasome","label":"Step: Hand over hand","section":"mechanism"}]},{"id":"proteasome-sealed-barrel-why","machine":"proteasome","kind":"qa","prompt":"The proteasome's cutting sites sit inside a sealed barrel, behind a gate that the motor opens. Why does the cell hide them there?","answer":"So only a chain fed through the gate meets them, and the cell's other proteins stay safe.","explanation":"Like a paper shredder with a doorman: only tagged proteins get in, and the blades are enclosed.","section":"mechanism","topic":"purpose","sources":["step:Cut into short peptides","stop:barrel","analogy:A paper shredder with a doorman"],"tags":["barrel","safety"],"difficulty":1,"url":"/machines/proteasome#mechanism","cites":[{"source":"step:Cut into short peptides","machine":"proteasome","label":"Step: Cut into short peptides","section":"mechanism"},{"source":"stop:barrel","machine":"proteasome","label":"Big picture: Inside the barrel","section":"story"},{"source":"analogy:A paper shredder with a doorman","machine":"proteasome","label":"Analogy: A paper shredder with a doorman","section":"story"}]},{"id":"proteasome-atp-cost","machine":"proteasome","kind":"qa","prompt":"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?","answer":"Dozens: about 50 to 80.","explanation":"It takes about 13 seconds per protein. ATP synthase makes the ATP the proteasome spends.","section":"evidence","topic":"numbers","sources":["evidence:atp-cost-ub5-dhfr","fact:P9","link:atp-synthase"],"tags":["energy","cost"],"difficulty":2,"url":"/machines/proteasome#evidence","cites":[{"source":"evidence:atp-cost-ub5-dhfr","machine":"proteasome","label":"ATP hydrolysed per ubiquitinated DHFR molecule degraded (Peth A 2013)","section":"evidence","anchor":"ev-atp-cost-ub5-dhfr"},{"source":"fact:P9","machine":"proteasome","label":"ATP spent to destroy one tagged protein: 50–80 ATP","section":"story"},{"source":"link:atp-synthase","machine":"proteasome","label":"Link to ATP synthase","section":"story"}]},{"id":"proteasome-vs-ribosome-rate","machine":"proteasome","kind":"qa","prompt":"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?","answer":"The proteasomes destroy about half as many proteins per minute as the ribosomes make.","explanation":"The amino acids from destroyed proteins feed the ribosomes again.","section":"story","topic":"numbers","sources":["link:ribosome","fact:P12","fact:P11"],"tags":["links","ribosome"],"difficulty":2,"url":"/machines/proteasome#story","cites":[{"source":"link:ribosome","machine":"proteasome","label":"Link to Ribosome","section":"story"},{"source":"fact:P12","machine":"proteasome","label":"Proteins destroyed per minute in one mouse cell: 2 × 10^6 per minute","section":"story"},{"source":"fact:P11","machine":"proteasome","label":"Proteasomes in one mouse cell: 8 × 10^5 proteasomes","section":"story"}]},{"id":"proteasome-pieces-fate","machine":"proteasome","kind":"qa","prompt":"Most of the short pieces the proteasome makes are recycled into new proteins. What happens to a few of them?","answer":"They go on display at the cell surface, where the immune system checks them.","explanation":"They are a sample of what the cell is making.","section":"story","topic":"purpose","sources":["stop:pieces","story:summary","fact:P8-mhc"],"tags":["immune"],"difficulty":1,"url":"/machines/proteasome#story","cites":[{"source":"stop:pieces","machine":"proteasome","label":"Big picture: The pieces","section":"story"},{"source":"story:summary","machine":"proteasome","label":"Big picture","section":"story"},{"source":"fact:P8-mhc","machine":"proteasome","label":"Length of the peptides shown on MHC class I: 8–10 amino acids","section":"story"}]},{"id":"proteasome-drug-myeloma","machine":"proteasome","kind":"qa","prompt":"The proteasome is also a drug target. The drug bortezomib blocks it. Which disease was this drug approved to treat?","answer":"Multiple myeloma, a blood cancer.","explanation":"It was the first proteasome drug approved in the US.","section":"story","topic":"purpose","sources":["fact:P15"],"tags":["medicine","drug"],"difficulty":2,"url":"/machines/proteasome#story","cites":[{"source":"fact:P15","machine":"proteasome","label":"US approval of bortezomib, the first proteasome drug: 13 May 2003","section":"story"}]},{"id":"proteasome-protac","machine":"proteasome","kind":"qa","prompt":"Drug designers now want the proteasome to destroy a protein of their own choice. How does a PROTAC molecule make that happen?","answer":"It ties the chosen protein to the enzyme that adds the ubiquitin tag, so the protein gets marked for destruction.","explanation":"Related tools, such as degradation tags, can remove a chosen protein within minutes.","section":"summary","topic":"debate","sources":["frontier:Targeted degradation with PROTACs","frontier:Engineered degradation tags"],"tags":["medicine","design"],"difficulty":2,"url":"/machines/proteasome#summary","cites":[{"source":"frontier:Targeted degradation with PROTACs","machine":"proteasome","label":"Open question: Targeted degradation with PROTACs","section":"summary"},{"source":"frontier:Engineered degradation tags","machine":"proteasome","label":"Open question: Engineered degradation tags","section":"summary"}]}]}