8IWW

hSPCA1 in the CaE1P-ADP state

Summary for 8IWW

• Entry DOI: 10.2210/pdb8iww/pdb
• EMDB information: 35781
• Descriptor: Calcium-transporting ATPase type 2C member 1, CALCIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: hspca1, membrane protein, metal transport
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 98377.05

Authors

Liu, Z.M.,Wu, M.Q.,Wu, C. (deposition date: 2023-03-31, release date: 2023-12-27, Last modification date: 2025-07-16)

Primary citation

Wu, M.,Wu, C.,Song, T.,Pan, K.,Wang, Y.,Liu, Z.
Structure and transport mechanism of the human calcium pump SPCA1.
Cell Res., 33:533-545, 2023

PubMed Abstract: 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.

PubMed: 37258749
DOI: 10.1038/s41422-023-00827-x

Experimental method

ELECTRON MICROSCOPY (3.71 Å)