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Structural and functional analysis of human pannexin 2 channel

Author

Listed:
  • Zhihui He

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Yonghui Zhao

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Michael J. Rau

    (Washington University Center for Cellular Imaging, Washington University School of Medicine)

  • James A. J. Fitzpatrick

    (Washington University School of Medicine
    Washington University Center for Cellular Imaging, Washington University School of Medicine
    Washington University School of Medicine
    Washington University in Saint Louis)

  • Rajan Sah

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Hongzhen Hu

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Peng Yuan

    (Washington University School of Medicine
    Washington University School of Medicine
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

The pannexin 2 channel (PANX2) participates in multiple physiological processes including skin homeostasis, neuronal development, and ischemia-induced brain injury. However, the molecular basis of PANX2 channel function remains largely unknown. Here, we present a cryo-electron microscopy structure of human PANX2, which reveals pore properties contrasting with those of the intensely studied paralog PANX1. The extracellular selectivity filter, defined by a ring of basic residues, more closely resembles that of the distantly related volume-regulated anion channel (VRAC) LRRC8A, rather than PANX1. Furthermore, we show that PANX2 displays a similar anion permeability sequence as VRAC, and that PANX2 channel activity is inhibited by a commonly used VRAC inhibitor, DCPIB. Thus, the shared channel properties between PANX2 and VRAC may complicate dissection of their cellular functions through pharmacological manipulation. Collectively, our structural and functional analysis provides a framework for development of PANX2-specific reagents that are needed for better understanding of channel physiology and pathophysiology.

Suggested Citation

  • Zhihui He & Yonghui Zhao & Michael J. Rau & James A. J. Fitzpatrick & Rajan Sah & Hongzhen Hu & Peng Yuan, 2023. "Structural and functional analysis of human pannexin 2 channel," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37413-z
    DOI: 10.1038/s41467-023-37413-z
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    1. Nazia Hussain & Ashish Apotikar & Shabareesh Pidathala & Sourajit Mukherjee & Ananth Prasad Burada & Sujit Kumar Sikdar & Kutti R. Vinothkumar & Aravind Penmatsa, 2024. "Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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