8F7C

Cryo-EM structure of human pannexin 2

Summary for 8F7C

• Entry DOI: 10.2210/pdb8f7c/pdb
• EMDB information: 28902
• Descriptor: Pannexin-2, Soluble cytochrome b562 fusion (1 entity in total)
• Functional Keywords: ion channel, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 385233.84

Authors

He, Z.,Yuan, P. (deposition date: 2022-11-18, release date: 2023-04-05, Last modification date: 2024-10-23)

Primary citation

He, Z.,Zhao, Y.,Rau, M.J.,Fitzpatrick, J.A.J.,Sah, R.,Hu, H.,Yuan, P.
Structural and functional analysis of human pannexin 2 channel.
Nat Commun, 14:1712-1712, 2023

PubMed 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.

PubMed: 36973289
DOI: 10.1038/s41467-023-37413-z

Experimental method

ELECTRON MICROSCOPY (3.92 Å)