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Papers of the Week

Papers: 28 Mar 2020 - 3 Apr 2020

Animal Studies, Human Studies

2020 Mar 30

Nat Struct Mol Biol

Cryo-EM structures of the ATP release channel pannexin 1.


Deng Z, He Z, Maksaev G, Bitter RM, Rau M, Fitzpatrick JAJ, Yuan P
Nat Struct Mol Biol. 2020 Mar 30.
PMID: 32231289.


The plasma membrane adenosine triphosphate (ATP) release channel pannexin 1 (PANX1) has been implicated in many physiological and pathophysiological processes associated with purinergic signaling, including cancer progression, apoptotic cell clearance, inflammation, blood pressure regulation, oocyte development, epilepsy and neuropathic pain. Here we present near-atomic-resolution structures of human and frog PANX1 determined by cryo-electron microscopy that revealed a heptameric channel architecture. Compatible with ATP permeation, the transmembrane pore and cytoplasmic vestibule were exceptionally wide. An extracellular tryptophan ring located at the outer pore created a constriction site, potentially functioning as a molecular sieve that restricts the size of permeable substrates. The amino and carboxyl termini, not resolved in the density map, appeared to be structurally dynamic and might contribute to narrowing of the pore during channel gating. In combination with functional characterization, this work elucidates the previously unknown architecture of pannexin channels and establishes a foundation for understanding their unique channel properties.