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TitleMultiple sub-state structures of SERCA2b reveal conformational overlap at transition steps during the catalytic cycle.
Journal, issue, pagesCell Rep, Vol. 41, Issue 10, Page 111760, Year 2022
Publish dateDec 6, 2022
AuthorsYuxia Zhang / Chigusa Kobayashi / Xiaohan Cai / Satoshi Watanabe / Akihisa Tsutsumi / Masahide Kikkawa / Yuji Sugita / Kenji Inaba /
PubMed AbstractSarco/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.
External linksCell Rep / PubMed:36476867
MethodsEM (single particle)
Resolution3.0 - 3.4 Å
Structure data

32347

7w7t

EMDB-32347, PDB-7w7t:
The E1-BeF3- 2Ca2+ of SERCA2b
Method: EM (single particle) / Resolution: 3.4 Å

32348

7w7u

EMDB-32348, PDB-7w7u:
The 'Ca2+-unbound' BeF3- of SERCA2b
Method: EM (single particle) / Resolution: 3.0 Å

32349

7w7v

EMDB-32349, PDB-7w7v:
'late' E2P of SERCA2b
Method: EM (single particle) / Resolution: 3.0 Å

32350

7w7w

EMDB-32350, PDB-7w7w:
E2 Pi of SERCA2b
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

ChemComp-MG:
Unknown entry

ChemComp-ALF:
TETRAFLUOROALUMINATE ION

Source
  • homo sapiens (human)
KeywordsMETAL TRANSPORT / calcium

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