Structure and transport mechanism of the human calcium pump SPCA1.

ABSTRACT: Secretory-pathway Ca²⁺-ATPases (SPCAs) play critical roles in maintaining Ca²⁺ homeostasis, but the exact mechanism of SPCAs-mediated Ca²⁺ 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 Ca²⁺ 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 Ca²⁺-binding site induced by the separation of transmembr

SUBMITTER: Wu M 

PROVIDER: S-EPMC10313705 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature