{"format":"molecular-machines.cards","version":1,"updated":"2026-10-01","decks":[{"machine":"serca","name":"SERCA calcium pump","count":28,"url":"/learn/cards/serca.json"}],"cards":[{"id":"serca-job","machine":"serca","kind":"qa","prompt":"What job does SERCA do in a muscle cell after each contraction?","answer":"It clears calcium from the cytoplasm, pumping it back into the sarcoplasmic reticulum.","explanation":"Calcium switches muscle on, so the muscle can only relax and fire again once SERCA has taken the calcium away.","section":"summary","topic":"purpose","sources":["machine:summary","stop:twitch"],"tags":["calcium","muscle"],"difficulty":1,"url":"/machines/serca#summary","cites":[{"source":"machine:summary","machine":"serca","label":"Summary","section":"summary"},{"source":"stop:twitch","machine":"serca","label":"Big picture: One twitch","section":"story"}]},{"id":"serca-ca-per-atp","machine":"serca","kind":"cloze","prompt":"SERCA burns one ATP to push {{two}} calcium ions out of the cytoplasm.","answer":"two","explanation":"The crystal structure shows two calcium sites side by side inside the membrane domain, which fits this ratio.","section":"summary","topic":"numbers","sources":["stat:Calcium ions per ATP","machine:tagline","ref:toyoshima2000"],"tags":["stoichiometry","atp"],"difficulty":1,"url":"/machines/serca#summary","cites":[{"source":"stat:Calcium ions per ATP","machine":"serca","label":"Key number: Calcium ions per ATP","section":"summary"},{"source":"machine:tagline","machine":"serca","label":"Summary","section":"summary"},{"source":"ref:toyoshima2000","machine":"serca","label":"Toyoshima et al.","section":"sources","anchor":"ref-toyoshima2000","href":"https://doi.org/10.1038/35015017"}]},{"id":"serca-p-domain","machine":"serca","kind":"qa","prompt":"Which SERCA domain holds the aspartate that accepts the phosphoryl group from ATP?","answer":"The P (phosphorylation) domain.","explanation":"The P domain has the same fold as haloacid dehalogenase, a general phosphotransfer scaffold.","section":"summary","topic":"parts","sources":["component:P domain","evolution:A borrowed catalytic core","ref:toyoshima2000"],"tags":["domains","phosphorylation"],"difficulty":1,"url":"/machines/serca#summary","cites":[{"source":"component:P domain","machine":"serca","label":"Part: P domain","section":"summary"},{"source":"evolution:A borrowed catalytic core","machine":"serca","label":"A borrowed catalytic core","section":"summary"},{"source":"ref:toyoshima2000","machine":"serca","label":"Toyoshima et al.","section":"sources","anchor":"ref-toyoshima2000","href":"https://doi.org/10.1038/35015017"}]},{"id":"serca-n-domain","machine":"serca","kind":"qa","prompt":"What part of ATP does SERCA's N domain bind?","answer":"The adenosine part.","explanation":"When nucleotide binds, the N domain swings onto the P domain, which holds the aspartate that takes the phosphate.","section":"summary","topic":"parts","sources":["component:N domain","evidence:three-cytoplasmic-domains"],"tags":["domains","atp"],"difficulty":2,"url":"/machines/serca#summary","cites":[{"source":"component:N domain","machine":"serca","label":"Part: N domain","section":"summary"},{"source":"evidence:three-cytoplasmic-domains","machine":"serca","label":"Cytoplasmic domains of SERCA1a (Toyoshima C 2000)","section":"evidence","anchor":"ev-three-cytoplasmic-domains"}]},{"id":"serca-a-domain","machine":"serca","kind":"qa","prompt":"What does SERCA's A (actuator) domain drive when it tilts against the membrane helices?","answer":"Gating and dephosphorylation.","explanation":"Release of ADP opens the lumenal gate and release of phosphate closes it, mainly through movements of the A domain.","section":"summary","topic":"parts","sources":["component:A domain","evidence:four-principal-states"],"tags":["domains","gating"],"difficulty":2,"url":"/machines/serca#summary","cites":[{"source":"component:A domain","machine":"serca","label":"Part: A domain","section":"summary"},{"source":"evidence:four-principal-states","machine":"serca","label":"Reaction-cycle states with atomic models (Toyoshima C 2004)","section":"evidence","anchor":"ev-four-principal-states"}]},{"id":"serca-phospholamban-role","machine":"serca","kind":"qa","prompt":"How does phospholamban change the cardiac SERCA pump?","answer":"It raises the calcium level the pump needs to cycle.","explanation":"Phospholamban is an inhibitory membrane micropeptide of cardiac muscle: the same pump rate then needs more calcium.","section":"summary","topic":"parts","sources":["component:phospholamban","ref:maclennan2003"],"tags":["regulation","heart"],"difficulty":2,"url":"/machines/serca#summary","cites":[{"source":"component:phospholamban","machine":"serca","label":"Part: phospholamban","section":"summary"},{"source":"ref:maclennan2003","machine":"serca","label":"MacLennan and Kranias, Nat Rev Mol Cell Biol 2003","section":"sources","anchor":"ref-maclennan2003","href":"https://doi.org/10.1038/nrm1151"}]},{"id":"serca-dworf-safer","machine":"serca","kind":"qa","prompt":"Why is the activator DWORF seen as a safer way to boost SERCA than removing phospholamban?","answer":"Complete loss of phospholamban is lethal in humans; DWORF instead raises turnover and competes phospholamban off its site.","explanation":"This is a lab-scale idea: DWORF is the only known activator in the regulin family.","section":"summary","topic":"debate","sources":["frontier:Activator instead of brake removal","ref:verry2026"],"tags":["heart-failure","regulation"],"difficulty":2,"url":"/machines/serca#summary","cites":[{"source":"frontier:Activator instead of brake removal","machine":"serca","label":"Open question: Activator instead of brake removal","section":"summary"},{"source":"ref:verry2026","machine":"serca","label":"Verry and Makarewich, Front Cell Dev Biol 2026","section":"sources","anchor":"ref-verry2026","href":"https://doi.org/10.3389/fcell.2026.1864847"}]},{"id":"serca-gene-transfer-status","machine":"serca","kind":"qa","prompt":"What is the state of SERCA2a gene transfer as a treatment for heart failure?","answer":"It restored contractile function in failing heart muscle, but clinical results have been inconsistent.","explanation":"SR calcium cycling and SERCA2a activity fall in heart failure. The approach is still rated lab-scale.","section":"summary","topic":"debate","sources":["frontier:Gene transfer for heart failure","ref:periasamy2007"],"tags":["heart-failure"],"difficulty":2,"url":"/machines/serca#summary","cites":[{"source":"frontier:Gene transfer for heart failure","machine":"serca","label":"Open question: Gene transfer for heart failure","section":"summary"},{"source":"ref:periasamy2007","machine":"serca","label":"Periasamy and Kalyanasundaram, Muscle Nerve 2007","section":"sources","anchor":"ref-periasamy2007","href":"https://doi.org/10.1002/mus.20745"}]},{"id":"serca-e1-magnesium","machine":"serca","kind":"qa","prompt":"In SERCA's calcium-free E1 state, one Mg2+ sits in a calcium site. What does it block until calcium arrives?","answer":"Phosphorylation.","explanation":"Calcium is the trigger: once the two high-affinity sites fill, phosphorylation can go ahead. In skeletal muscle, sarcolipin stabilises this E1 state with magnesium.","section":"mechanism","topic":"cycle","sources":["mechanism:E1 waits with magnesium","component:sarcolipin","ref:toyoshima2013"],"tags":["e1","magnesium"],"difficulty":2,"url":"/machines/serca#mechanism","cites":[{"source":"mechanism:E1 waits with magnesium","machine":"serca","label":"Step: E1 waits with magnesium","section":"mechanism"},{"source":"component:sarcolipin","machine":"serca","label":"Part: sarcolipin","section":"summary"},{"source":"ref:toyoshima2013","machine":"serca","label":"Toyoshima et al.","section":"sources","anchor":"ref-toyoshima2013","href":"https://doi.org/10.1038/nature11899"}]},{"id":"serca-atp-bridges","machine":"serca","kind":"qa","prompt":"What does ATP binding do to SERCA's N and P domains?","answer":"It bridges them, pulling the widely separated domains together.","explanation":"The A domain then tilts and one membrane helix moves to lock the cytoplasmic gate, occluding the two calcium ions.","section":"mechanism","topic":"cycle","sources":["mechanism:ATP bridges the N and P domains","ref:toyoshima2004atp"],"tags":["atp","domains"],"difficulty":2,"url":"/machines/serca#mechanism","cites":[{"source":"mechanism:ATP bridges the N and P domains","machine":"serca","label":"Step: ATP bridges the N and P domains","section":"mechanism"},{"source":"ref:toyoshima2004atp","machine":"serca","label":"Toyoshima et al.","section":"sources","anchor":"ref-toyoshima2004atp","href":"https://doi.org/10.1038/nature02680"}]},{"id":"serca-no-backflow","machine":"serca","kind":"qa","prompt":"When SERCA phosphorylates itself, what stops the bound calcium from flowing back to the cytoplasm?","answer":"Helices M1 and M2 shift and close the cytosolic entrance.","explanation":"The same movement that transfers the phosphate to the aspartate shuts the entry door, so the ions are trapped before the exit opens.","section":"mechanism","topic":"cycle","sources":["mechanism:The pump phosphorylates itself","ref:sorensen2004"],"tags":["gating","phosphorylation"],"difficulty":2,"url":"/machines/serca#mechanism","cites":[{"source":"mechanism:The pump phosphorylates itself","machine":"serca","label":"Step: The pump phosphorylates itself","section":"mechanism"},{"source":"ref:sorensen2004","machine":"serca","label":"Sorensen et al.","section":"sources","anchor":"ref-sorensen2004","href":"https://doi.org/10.1126/science.1099366"}]},{"id":"serca-lumenal-gate-trigger","machine":"serca","kind":"cloze","prompt":"In SERCA, the change from E1P to E2P after {{phosphorylation}} opens the exit path for calcium to the lumen.","answer":"phosphorylation","explanation":"Helices M1 to M6 open the path, and a shift of M4 exposes Glu 309, Glu 771 and Asn 796 to the lumen, where calcium leaves.","section":"mechanism","topic":"cycle","sources":["mechanism:The lumenal gate opens and calcium leaves","ref:olesen2007"],"tags":["gating","e2p"],"difficulty":2,"url":"/machines/serca#mechanism","cites":[{"source":"mechanism:The lumenal gate opens and calcium leaves","machine":"serca","label":"Step: The lumenal gate opens and calcium leaves","section":"mechanism"},{"source":"ref:olesen2007","machine":"serca","label":"Olesen et al.","section":"sources","anchor":"ref-olesen2007","href":"https://doi.org/10.1038/nature06418"}]},{"id":"serca-protons-empty-sites","machine":"serca","kind":"qa","prompt":"After SERCA releases its two calcium ions to the lumen, what binds the empty sites?","answer":"Protons, which become occluded.","explanation":"The pump carries protons back the other way; then the phosphoenzyme is hydrolysed and the cycle can reset.","section":"mechanism","topic":"cycle","sources":["mechanism:Protons take the empty seats","ref:olesen2004"],"tags":["protons","counter-transport"],"difficulty":2,"url":"/machines/serca#mechanism","cites":[{"source":"mechanism:Protons take the empty seats","machine":"serca","label":"Step: Protons take the empty seats","section":"mechanism"},{"source":"ref:olesen2004","machine":"serca","label":"Olesen et al.","section":"sources","anchor":"ref-olesen2004","href":"https://doi.org/10.1126/science.1106289"}]},{"id":"serca-tges-motif","machine":"serca","kind":"cloze","prompt":"SERCA's phosphoenzyme is hydrolysed through the conserved {{Thr-Gly-Glu-Ser}} motif, by the same associative chemistry as the forward transfer.","answer":"Thr-Gly-Glu-Ser","explanation":"This motif (TGES) lets water attack the phosphate while the counter-transported protons stay occluded.","section":"mechanism","topic":"cycle","sources":["mechanism:Protons take the empty seats","evidence:counterion-occlusion","ref:olesen2004"],"tags":["dephosphorylation"],"difficulty":3,"url":"/machines/serca#mechanism","cites":[{"source":"mechanism:Protons take the empty seats","machine":"serca","label":"Step: Protons take the empty seats","section":"mechanism"},{"source":"evidence:counterion-occlusion","machine":"serca","label":"State in which the counter-transported protons are occluded (Olesen C 2004)","section":"evidence","anchor":"ev-counterion-occlusion"},{"source":"ref:olesen2004","machine":"serca","label":"Olesen et al.","section":"sources","anchor":"ref-olesen2004","href":"https://doi.org/10.1126/science.1106289"}]},{"id":"serca-e2-headpiece","machine":"serca","kind":"cloze","prompt":"In SERCA's calcium-free E2 state, the three cytoplasmic domains gather into {{one compact headpiece}}.","answer":"one compact headpiece","explanation":"Without nucleotide in E1 they sit far apart; between the states, six of the ten membrane helices rearrange.","section":"mechanism","topic":"cycle","sources":["mechanism:E2 relaxes back to E1","evidence:e2-thapsigargin-structure","ref:toyoshima2002"],"tags":["e2","domains"],"difficulty":2,"url":"/machines/serca#mechanism","cites":[{"source":"mechanism:E2 relaxes back to E1","machine":"serca","label":"Step: E2 relaxes back to E1","section":"mechanism"},{"source":"evidence:e2-thapsigargin-structure","machine":"serca","label":"Changes from the Ca2+-bound E1 state to the Ca2+-free E2 state (Toyoshima C 2002)","section":"evidence","anchor":"ev-e2-thapsigargin-structure"},{"source":"ref:toyoshima2002","machine":"serca","label":"Toyoshima and Nomura, Nature 2002","section":"sources","anchor":"ref-toyoshima2002","href":"https://doi.org/10.1038/nature00944"}]},{"id":"serca-gradient-size","machine":"serca","kind":"cloze","prompt":"At rest, the SERCA pumps hold about {{4,000}} times more free calcium inside the sarcoplasmic reticulum than in the muscle cytosol.","answer":"4,000","explanation":"Calculated from free Ca2+ of about 390 µM in the SR and about 100 nM in the cytosol of mouse fibres. The often-quoted 10,000-fold is outside the cell versus the cytosol.","section":"story","topic":"numbers","sources":["fact:S4","ref:ziman2010"],"tags":["gradient","calcium"],"difficulty":2,"url":"/machines/serca#story","cites":[{"source":"fact:S4","machine":"serca","label":"Calcium gradient across the SR membrane: 4,000 times","section":"story"},{"source":"ref:ziman2010","machine":"serca","label":"Ziman 2010","section":"sources","href":"https://doi.org/10.1016/j.bpj.2010.08.032"}]},{"id":"serca-atp-pays","machine":"serca","kind":"qa","prompt":"Why is one ATP enough to pay for SERCA pushing two calcium ions up the SR gradient?","answer":"The push costs about 43 kJ/mol, and one ATP supplies 57–64 kJ/mol in the cell.","explanation":"The 43 kJ/mol is 2 × RT × ln(3,900) at 37 °C; it leaves out any voltage across the SR membrane.","section":"story","topic":"numbers","sources":["fact:S8","ref:bnid100775"],"tags":["energy","atp"],"difficulty":3,"url":"/machines/serca#story","cites":[{"source":"fact:S8","machine":"serca","label":"Energy to push two calcium ions up the gradient: 43 kJ/mol","section":"story"},{"source":"ref:bnid100775","machine":"serca","label":"BNID 100775","section":"sources","href":"https://bionumbers.hms.harvard.edu/bionumber.aspx?id=100775"}]},{"id":"serca-resting-oxygen","machine":"serca","kind":"cloze","prompt":"In resting mouse muscle, SERCA accounts for about {{40–50%}} of the muscle's oxygen use.","answer":"40–50%","explanation":"Measured in isolated mouse muscles at 30 °C. The authors scale this to 12–15% of whole-body resting oxygen use, an estimate.","section":"story","topic":"numbers","sources":["fact:S9","ref:smith2013"],"tags":["energy","metabolism"],"difficulty":2,"url":"/machines/serca#story","cites":[{"source":"fact:S9","machine":"serca","label":"Share of resting muscle oxygen use spent on SERCA: 40–50 %","section":"story"},{"source":"ref:smith2013","machine":"serca","label":"Smith 2013","section":"sources","href":"https://doi.org/10.1371/journal.pone.0068924"}]},{"id":"serca-heart-share","machine":"serca","kind":"cloze","prompt":"In mouse heart muscle cells, SERCA removes about {{90%}} of each beat's calcium.","answer":"90%","explanation":"The sodium-calcium exchanger removes most of the rest (9%), so SERCA sets how fast the heart relaxes.","section":"story","topic":"numbers","sources":["fact:S5","ref:li1998"],"tags":["heart","calcium"],"difficulty":2,"url":"/machines/serca#story","cites":[{"source":"fact:S5","machine":"serca","label":"Share of each beat's calcium that SERCA removes: 90 %","section":"story"},{"source":"ref:li1998","machine":"serca","label":"Li 1998","section":"sources","href":"https://doi.org/10.1152/ajpheart.1998.274.4.h1335"}]},{"id":"serca-airlock-breaks","machine":"serca","kind":"qa","prompt":"SERCA is often compared to an airlock whose two doors never open together. Where does that analogy break?","answer":"An airlock is passive; the energy of ATP drives SERCA's doors.","explanation":"The analogy gets the gating right: because the two gates never open at once, the store cannot leak back.","section":"story","topic":"purpose","sources":["analogy:An airlock"],"tags":["analogy","gating"],"difficulty":2,"url":"/machines/serca#story","cites":[{"source":"analogy:An airlock","machine":"serca","label":"Analogy: An airlock","section":"story"}]},{"id":"serca-myosin-link","machine":"serca","kind":"qa","prompt":"How does SERCA switch myosin off at the end of a contraction?","answer":"It takes away the calcium that switched myosin on.","explanation":"SERCA is the off switch for the calcium signal that myosin, the consumer, responds to.","section":"story","topic":"purpose","sources":["link:myosin"],"tags":["myosin","contraction"],"difficulty":1,"url":"/machines/serca#story","cites":[{"source":"link:myosin","machine":"serca","label":"Link to Myosin","section":"story"}]},{"id":"serca-ratio-method","machine":"serca","kind":"qa","prompt":"How did Yu and Inesi (1995) measure SERCA's calcium-per-ATP ratio?","answer":"By following 45Ca2+ uptake and Ca2+-dependent phosphate release side by side in native rabbit SR vesicles.","explanation":"At the start of pumping, close to two calcium ions went in for each ATP split, and the ratio was never seen above 2.","section":"evidence","topic":"numbers","sources":["evidence:calcium-per-atp-coupling"],"tags":["stoichiometry","method"],"difficulty":3,"url":"/machines/serca#evidence","cites":[{"source":"evidence:calcium-per-atp-coupling","machine":"serca","label":"Ca2+ transported per ATP hydrolysed (Yu X 1995)","section":"evidence","anchor":"ev-calcium-per-atp-coupling"}]},{"id":"serca-ratio-best-case","machine":"serca","kind":"qa","prompt":"Why is two calcium ions per ATP the best case for SERCA rather than a fixed rule?","answer":"The ratio falls as calcium builds up inside the vesicles.","explanation":"With oxalate clamping lumenal calcium, the steady ratio was about 1.5.","section":"evidence","topic":"numbers","sources":["evidence:calcium-per-atp-coupling","evidence:coupling-falls-with-lumenal-calcium"],"tags":["stoichiometry","coupling"],"difficulty":2,"url":"/machines/serca#evidence","cites":[{"source":"evidence:calcium-per-atp-coupling","machine":"serca","label":"Ca2+ transported per ATP hydrolysed (Yu X 1995)","section":"evidence","anchor":"ev-calcium-per-atp-coupling"},{"source":"evidence:coupling-falls-with-lumenal-calcium","machine":"serca","label":"Ca2+/ATP coupling as lumenal Ca2+ rises (Yu X 1995)","section":"evidence","anchor":"ev-coupling-falls-with-lumenal-calcium"}]},{"id":"serca-plateau-not-leak","machine":"serca","kind":"qa","prompt":"After SERCA's calcium uptake into vesicles levelled off, ATP splitting went on. Thapsigargin stopped it, and no calcium leaked out. What did this show?","answer":"The extra ATP went to pumps cycling without moving calcium, not to re-pumping leaked calcium.","explanation":"Lumenal calcium slows the pump itself, so back-inhibition, not leak, limits the gradient SERCA can build.","section":"evidence","topic":"numbers","sources":["evidence:coupling-falls-with-lumenal-calcium","evidence:lumenal-calcium-level"],"tags":["coupling","gradient"],"difficulty":3,"url":"/machines/serca#evidence","cites":[{"source":"evidence:coupling-falls-with-lumenal-calcium","machine":"serca","label":"Ca2+/ATP coupling as lumenal Ca2+ rises (Yu X 1995)","section":"evidence","anchor":"ev-coupling-falls-with-lumenal-calcium"},{"source":"evidence:lumenal-calcium-level","machine":"serca","label":"Lumenal Ca2+ concentration reached by the pump (Yu X 1993)","section":"evidence","anchor":"ev-lumenal-calcium-level"}]},{"id":"serca-proton-ratio","machine":"serca","kind":"cloze","prompt":"In reconstituted proteoliposomes, SERCA moved {{1}} H+ out of the lumen for each Ca2+ moved in.","answer":"1","explanation":"Yu and colleagues (1993) read calcium with murexide and lumenal pH with trapped pyranine; the two traces ran in parallel for 10 minutes. Earlier studies gave 1.0–1.5.","section":"evidence","topic":"numbers","sources":["evidence:proton-countertransport","stat:Proton counter-transport","ref:yu1993"],"tags":["protons","counter-transport"],"difficulty":2,"url":"/machines/serca#evidence","cites":[{"source":"evidence:proton-countertransport","machine":"serca","label":"H+ moved out per Ca2+ moved in (Yu X 1993)","section":"evidence","anchor":"ev-proton-countertransport"},{"source":"stat:Proton counter-transport","machine":"serca","label":"Key number: Proton counter-transport","section":"summary"},{"source":"ref:yu1993","machine":"serca","label":"Yu et al.","section":"sources","anchor":"ref-yu1993","href":"https://doi.org/10.1016/s0006-3495(93)81489-9"}]},{"id":"serca-pln-max-rate","machine":"serca","kind":"qa","prompt":"When purified phospholamban was added to SERCA, how did it change the pump's ATP splitting?","answer":"It shifted the calcium curve to higher calcium (KCa 0.26 to 0.62 µM) without lowering the maximal rate.","explanation":"Phospholamban is a brake on calcium affinity, not on top speed; the superinhibitory mutant PLB4 shifted KCa further, to 1.38 µM.","section":"evidence","topic":"numbers","sources":["evidence:phospholamban-calcium-affinity","ref:akin2013"],"tags":["phospholamban","regulation"],"difficulty":3,"url":"/machines/serca#evidence","cites":[{"source":"evidence:phospholamban-calcium-affinity","machine":"serca","label":"Apparent Ca2+ affinity of the pump (KCa for half-maximal ATPase) with and without phospholamban (Akin BL 2013)","section":"evidence","anchor":"ev-phospholamban-calcium-affinity"},{"source":"ref:akin2013","machine":"serca","label":"Akin et al.","section":"sources","anchor":"ref-akin2013","href":"https://doi.org/10.1074/jbc.M113.501585"}]},{"id":"serca-thapsigargin-tool","machine":"serca","kind":"qa","prompt":"Why did thapsigargin become a standard tool for blocking SERCA?","answer":"It inhibits SERCA's calcium uptake at sub-nanomolar doses but leaves calcium release channels and the plasma-membrane calcium pump unaffected.","explanation":"Free thapsigargin at 0.1 nM already inhibits uptake in SR vesicles; it binds the calcium-free pump and blocks calcium binding.","section":"evidence","topic":"numbers","sources":["evidence:thapsigargin-subnanomolar","stat:Thapsigargin inhibition","ref:sagara1991"],"tags":["thapsigargin","inhibitor"],"difficulty":2,"url":"/machines/serca#evidence","cites":[{"source":"evidence:thapsigargin-subnanomolar","machine":"serca","label":"Lowest free thapsigargin concentration that inhibits Ca2+ uptake (Sagara Y 1991)","section":"evidence","anchor":"ev-thapsigargin-subnanomolar"},{"source":"stat:Thapsigargin inhibition","machine":"serca","label":"Key number: Thapsigargin inhibition","section":"summary"},{"source":"ref:sagara1991","machine":"serca","label":"Sagara and Inesi, J Biol Chem 1991","section":"sources","anchor":"ref-sagara1991","href":"https://doi.org/10.1016/s0021-9258(18)92726-2"}]},{"id":"serca-monomer-method","machine":"serca","kind":"qa","prompt":"How did Heegaard and colleagues show that a single SERCA chain can pump calcium on its own?","answer":"In lipid-rich vesicles that still pumped, freeze-fracture EM counted one membrane particle per chain, and cross-linking found no pump pairs.","explanation":"So one polypeptide is the working unit; regulators such as phospholamban bind from the membrane.","section":"evidence","topic":"parts","sources":["evidence:monomer-transports-calcium","stat:Chains in the working unit","ref:heegaard1990"],"tags":["monomer","method"],"difficulty":3,"url":"/machines/serca#evidence","cites":[{"source":"evidence:monomer-transports-calcium","machine":"serca","label":"Oligomeric state of a pump that transports Ca2+ (Heegaard CW 1990)","section":"evidence","anchor":"ev-monomer-transports-calcium"},{"source":"stat:Chains in the working unit","machine":"serca","label":"Key number: Chains in the working unit","section":"summary"},{"source":"ref:heegaard1990","machine":"serca","label":"Heegaard et al.","section":"sources","anchor":"ref-heegaard1990","href":"https://doi.org/10.1016/S0021-9258(19)38502-3"}]}]}