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

Author

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  • Deshun Gong

    (Tsinghua University)

  • Ximin Chi

    (Tsinghua University)

  • Kang Ren

    (Tsinghua University)

  • Gaoxingyu Huang

    (Tsinghua University)

  • Gewei Zhou

    (Tsinghua University)

  • Nieng Yan

    (Tsinghua University
    Princeton University)

  • Jianlin Lei

    (Tsinghua University)

  • Qiang Zhou

    (Tsinghua University)

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.

Suggested Citation

  • Deshun Gong & Ximin Chi & Kang Ren & Gaoxingyu Huang & Gewei Zhou & Nieng Yan & Jianlin Lei & Qiang Zhou, 2018. "Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06075-7
    DOI: 10.1038/s41467-018-06075-7
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    Cited by:

    1. Adam Institoris & Milène Vandal & Govind Peringod & Christy Catalano & Cam Ha Tran & Xinzhu Yu & Frank Visser & Cheryl Breiteneder & Leonardo Molina & Baljit S. Khakh & Minh Dang Nguyen & Roger J. Tho, 2022. "Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Yafei Yuan & Fang Kong & Hanwen Xu & Angqi Zhu & Nieng Yan & Chuangye Yan, 2022. "Cryo-EM structure of human glucose transporter GLUT4," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

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