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Title | Multiple sub-state structures of SERCA2b reveal conformational overlap at transition steps during the catalytic cycle. |
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Journal, issue, pages | Cell Rep, Vol. 41, Issue 10, Page 111760, Year 2022 |
Publish date | Dec 6, 2022 |
![]() | Yuxia Zhang / Chigusa Kobayashi / Xiaohan Cai / Satoshi Watanabe / Akihisa Tsutsumi / Masahide Kikkawa / Yuji Sugita / Kenji Inaba / ![]() |
PubMed Abstract | Sarco/endoplasmic reticulum Ca ATPase (SERCA) pumps Ca into the endoplasmic reticulum (ER). Herein, we present cryo-electron microscopy (EM) structures of three intermediates of SERCA2b: Ca-bound ...Sarco/endoplasmic reticulum Ca ATPase (SERCA) pumps Ca into the endoplasmic reticulum (ER). Herein, we present cryo-electron microscopy (EM) structures of three intermediates of SERCA2b: Ca-bound phosphorylated (E1P·2Ca) and Ca-unbound dephosphorylated (E2·Pi) intermediates and another between the E2P and E2·Pi states. Our cryo-EM analysis demonstrates that the E1P·2Ca state exists in low abundance and preferentially transitions to an E2P-like structure by releasing Ca and that the Ca release gate subsequently undergoes stepwise closure during the dephosphorylation processes. Importantly, each intermediate adopts multiple sub-state structures including those like the next one in the catalytic series, indicating conformational overlap at transition steps, as further substantiated by atomistic molecular dynamic simulations of SERCA2b in a lipid bilayer. The present findings provide insight into how enzymes accelerate catalytic cycles. |
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Methods | EM (single particle) |
Resolution | 3.0 - 3.4 Å |
Structure data | EMDB-32347, PDB-7w7t: EMDB-32348, PDB-7w7u: EMDB-32349, PDB-7w7v: EMDB-32350, PDB-7w7w: |
Chemicals | ![]() ChemComp-CA: ![]() ChemComp-BEF: ![]() ChemComp-MG: ![]() ChemComp-ALF: |
Source |
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![]() | METAL TRANSPORT / ![]() |