8f7c | pdb_00008f7c
Cryo-EM structure of human pannexin 2
Structural highlights
FunctionC562_ECOLX Electron-transport protein of unknown function.PANX2_HUMAN Ion channel with a slight anion preference (PubMed:36973289). Also able to release ATP (PubMed:36869038). Plays a role in regulating neurogenesis and apoptosis in keratinocytes (By similarity).[UniProtKB:Q6IMP4][1] [2] Publication Abstract from PubMedThe 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. Structural and functional analysis of human pannexin 2 channel.,He Z, Zhao Y, Rau MJ, Fitzpatrick JAJ, Sah R, Hu H, Yuan P Nat Commun. 2023 Mar 27;14(1):1712. doi: 10.1038/s41467-023-37413-z. PMID:36973289[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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