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-Structure paper
タイトル | Structure and transport mechanism of the human calcium pump SPCA1. |
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ジャーナル・号・ページ | Cell Res, Vol. 33, Issue 7, Page 533-545, Year 2023 |
掲載日 | 2023年5月31日 |
著者 | Mengqi Wu / Cang Wu / Tiefeng Song / Kewu Pan / Yong Wang / Zhongmin Liu / |
PubMed 要旨 | 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 ...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. |
リンク | Cell Res / PubMed:37258749 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.25 - 3.71 Å |
構造データ | EMDB-35776, PDB-8iwp: EMDB-35777, PDB-8iwr: EMDB-35778, PDB-8iws: EMDB-35779, PDB-8iwt: EMDB-35780, PDB-8iwu: EMDB-35781, PDB-8iww: |
化合物 | ChemComp-CA: ChemComp-MG: ChemComp-ACP: ChemComp-BEF: ChemComp-ALF: ChemComp-ADP: |
由来 |
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キーワード | METAL TRANSPORT / hSPCA1 / MEMBRANE PROTEIN |