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Cryo-EM structure of TMEM63C suggests it functions as a monomer

Author

Listed:
  • Yuqi Qin

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Daqi Yu

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Dan Wu

    (Nanjing University)

  • Jiangqing Dong

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • William Thomas Li

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Chang Ye

    (Nanjing University)

  • Kai Chit Cheung

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Yingyi Zhang

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Yun Xu

    (Nanjing University)

  • YongQiang Wang

    (University of California)

  • Yun Stone Shi

    (Nanjing University
    Guangdong Institute of Intelligence Science and Technology)

  • Shangyu Dang

    (The Hong Kong University of Science and Technology, Clear Water Bay
    Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou)
    HKUST-Shenzhen Research Institute)

Abstract

The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.

Suggested Citation

  • Yuqi Qin & Daqi Yu & Dan Wu & Jiangqing Dong & William Thomas Li & Chang Ye & Kai Chit Cheung & Yingyi Zhang & Yun Xu & YongQiang Wang & Yun Stone Shi & Shangyu Dang, 2023. "Cryo-EM structure of TMEM63C suggests it functions as a monomer," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42956-2
    DOI: 10.1038/s41467-023-42956-2
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