RT Journal Article
SR Electronic
T1 Cryo-EM structures of the ATP release channel pannexin 1
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.05.895235
DO 10.1101/2020.01.05.895235
A1 Zengqin Deng
A1 Zhihui He
A1 Grigory Maksaev
A1 Ryan M. Bitter
A1 Michael Rau
A1 James A.J. Fitzpatrick
A1 Peng Yuan
YR 2020
UL http://biorxiv.org/content/early/2020/01/06/2020.01.05.895235.abstract
AB The plasma membrane ATP release channel pannexin 1 has been implicated in numerous 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 Xenopus tropicalis and Homo sapiens PANX1 determined by cryo-electron microscopy that reveal a heptameric channel architecture. Compatible with ATP permeation, the transmembrane pore and cytoplasmic vestibule are exceptionally wide. An extracellular tryptophan ring located at the outer pore creates a constriction site, potentially functioning as a molecular sieve that restricts the size of permeable substrates. 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 as well as for developing rational therapies.