Related Experiment Video

Updated: Aug 8, 2025

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
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Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

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Cryo-EM structure of human heptameric pannexin 2 channel

Hang Zhang1, Shiyu Wang2, Zhenzhen Zhang1

  • 1Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.

Nature Communications
|March 3, 2023
PubMed

Insights

The first high-resolution structure of Pannexin 2 (Panx2) reveals an open channel state. This structure elucidates the molecular mechanism of Panx2 channel gating and ATP permeation.

Area of Science:

  • Structural Biology
  • Molecular Physiology
  • Biophysics

Background:

  • Pannexin 2 (Panx2) is a large-pore channel involved in inflammation, energy production, and apoptosis.
  • Panx2 dysfunction is linked to neurological diseases like ischemic brain injury and gliomas.
  • The precise working mechanism of Panx2 has remained largely unknown.

Purpose of the Study:

  • To determine the high-resolution structure of human Pannexin 2.
  • To elucidate the molecular mechanism underlying Panx2 channel gating and function.
  • To provide insights into Panx2's role in physiological and pathological processes.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of human Panx2 at 3.4 Å resolution.
  • Comparative analysis with Pannexin 1 structures.
  • Molecular dynamics (MD) simulations.
  • ATP release assays.

Main Results:

  • The human Panx2 structure reveals a heptameric assembly with a wide channel pore, consistent with ATP permeation.
  • The Panx2 structure represents an open channel state, distinct from other Pannexin family members.
  • A critical molecular filter, formed by seven arginine residues at the extracellular entrance, controls substrate permeation.
  • MD simulations and functional assays validated the role of this filter in regulating ATP release.

Conclusions:

  • The study presents the cryo-EM structure of human Panx2, revealing its architecture and an open channel conformation.
  • The identified arginine ring acts as a key molecular filter, governing the channel's selectivity and function.
  • These findings offer crucial insights into the gating mechanism and substrate permeation of Panx2, advancing our understanding of its physiological and pathological roles.

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