Structure and transport mechanism of the human calcium pump SPCA1
|Corresponding Author||Wang，Yong; Liu，Zhongmin|
|Joint first author||Wu，Mengqi; Wu，Cang; Song，Tiefeng|
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.
First ; 共同第一 ; Corresponding
National Natural~Science Foundation of China ; Shenzhen Municipal Basic Research projects[JCYJ20210324105007020] ; National Key R&D Program of China[2021YFF1200404] ; Fundamental Research Funds for the Central Universities of China[K20220228]
|WOS Research Area|
|WOS Accession No|
|ESI Research Field|
MOLECULAR BIOLOGY & GENETICS
Cited Times [WOS]:0
|Document Type||Journal Article|
|Department||Department of Immunology and Microbiology|
1.Department of Immunology and Microbiology,School of Life Sciences,Southern University of Science and Technology,Shenzhen,Guangdong,China
2.College of Life Sciences,Zhejiang University,Hangzhou,Zhejiang,China
3.School of Biomedical Sciences,The Chinese University of Hong Kong,Hong Kong
4.The Provincial International Science and Technology Cooperation Base on Engineering Biology,Haining,International Campus of Zhejiang University, Zhejiang,China
|First Author Affilication||Department of Immunology and Microbiology; School of Life Sciences|
|Corresponding Author Affilication||Department of Immunology and Microbiology; School of Life Sciences|
|First Author's First Affilication||Department of Immunology and Microbiology; School of Life Sciences|
Wu，Mengqi,Wu，Cang,Song，Tiefeng,et al. Structure and transport mechanism of the human calcium pump SPCA1[J]. Cell Research,2023,33(7):533-545.
Wu，Mengqi,Wu，Cang,Song，Tiefeng,Pan，Kewu,Wang，Yong,&Liu，Zhongmin.(2023).Structure and transport mechanism of the human calcium pump SPCA1.Cell Research,33(7),533-545.
Wu，Mengqi,et al."Structure and transport mechanism of the human calcium pump SPCA1".Cell Research 33.7(2023):533-545.
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