2. Academic Validation
  3. Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin

Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin

  • Nat Commun. 2018 Sep 6;9(1):3623. doi: 10.1038/s41467-018-06075-7.
Deshun Gong 1,  Ximin Chi 2,  Kang Ren 2,  Gaoxingyu Huang 2,  Gewei Zhou 2,  Nieng Yan 2 3,  Jianlin Lei 4,  Qiang Zhou 5
Affiliations

Affiliations

  • 1 Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. dsgong@tsinghua.edu.cn.
  • 2 Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
  • 3 Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
  • 4 Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
  • 5 Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China. zhouqiang00@tsinghua.org.cn.
PMID: 30190470 DOI: 10.1038/s41467-018-06075-7
Abstract

Plasma membrane CA2+-ATPases (PMCAs) are key regulators of global CA2+ homeostasis and local intracellular CA2+ dynamics. Recently, Neuroplastin (NPTN) and basigin were identified as previously unrecognized obligatory subunits of PMCAs that dramatically increase the efficiency of PMCA-mediated CA2+ clearance. Here, we report the cryo-EM structure of human PMCA1 (hPMCA1) in complex with NPTN at a resolution of 4.1 Å for the overall structure and 3.9 Å for the transmembrane domain. The single transmembrane helix of NPTN interacts with the TM8-9-linker and TM10 of hPMCA1. The subunits are required for the hPMCA1 functional activity. The NPTN-bound hPMCA1 closely resembles the E1-Mg2+ structure of endo(sarco)plasmic reticulum CA2+ ATPase and the CA2+ site is exposed through a large open cytoplasmic pathway. This structure provides insight into how the subunits bind to the PMCAs and serves as an important basis for understanding the functional mechanisms of this essential calcium pump family.

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