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Structure paper

TitleStructure and transport mechanism of the human calcium pump SPCA1.
Journal, issue, pagesCell Res, Vol. 33, Issue 7, Page 533-545, Year 2023
Publish dateMay 31, 2023
AuthorsMengqi Wu / Cang Wu / Tiefeng Song / Kewu Pan / Yong Wang / Zhongmin Liu /
PubMed AbstractSecretory-pathway Ca-ATPases (SPCAs) play critical roles in maintaining Ca homeostasis, but the exact mechanism of SPCAs-mediated Ca transport remains unclear. Here, we determined six cryo-electron ...Secretory-pathway Ca-ATPases (SPCAs) play critical roles in maintaining Ca homeostasis, but the exact mechanism of SPCAs-mediated Ca transport remains unclear. Here, we determined six cryo-electron microscopy (cryo-EM) structures of human SPCA1 (hSPCA1) in a series of intermediate states, revealing a near-complete conformational cycle. With the aid of molecular dynamics simulations, these structures offer a clear structural basis for Ca entry and release in hSPCA1. We found that hSPCA1 undergoes unique conformational changes during ATP binding and phosphorylation compared to other well-studied P-type II ATPases. In addition, we observed a conformational distortion of the Ca-binding site induced by the separation of transmembrane helices 4L and 6, unveiling a distinct Ca release mechanism. Particularly, we determined a structure of the long-sought CaE2P state of P-type IIA ATPases, providing valuable insights into the Ca transport cycle. Together, these findings enhance our understanding of Ca transport by hSPCA1 and broaden our knowledge of P-type ATPases.
External linksCell Res / PubMed:37258749 / PubMed Central
MethodsEM (single particle)
Resolution3.25 - 3.71 Å
Structure data

35776

8iwp

EMDB-35776, PDB-8iwp:
hSPCA1 in the CaE1 state
Method: EM (single particle) / Resolution: 3.59 Å

35777

8iwr

EMDB-35777, PDB-8iwr:
hSPCA1 in the CaE1-ATP state
Method: EM (single particle) / Resolution: 3.52 Å

35778

8iws

EMDB-35778, PDB-8iws:
hSPCA1 in the CaE2P state
Method: EM (single particle) / Resolution: 3.42 Å

35779

8iwt

EMDB-35779, PDB-8iwt:
hSPCA1 in the early E2P state
Method: EM (single particle) / Resolution: 3.25 Å

35780

8iwu

EMDB-35780, PDB-8iwu:
hSPCA1 in the E2~P state
Method: EM (single particle) / Resolution: 3.31 Å

35781

8iww

EMDB-35781, PDB-8iww:
hSPCA1 in the CaE1P-ADP state
Method: EM (single particle) / Resolution: 3.71 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-ACP:
PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / AMP-PCP, energy-carrying molecule analogue*YM

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

ChemComp-ALF:
TETRAFLUOROALUMINATE ION

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • homo sapiens (human)
KeywordsMETAL TRANSPORT / hSPCA1 / MEMBRANE PROTEIN

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