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TitleCryo-EM structures of the ATP release channel pannexin 1.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 4, Page 373-381, Year 2020
Publish dateMar 30, 2020
AuthorsZengqin Deng / Zhihui He / Grigory Maksaev / Ryan M Bitter / Michael Rau / James A J Fitzpatrick / Peng Yuan /
PubMed AbstractThe plasma membrane adenosine triphosphate (ATP) release channel pannexin 1 (PANX1) has been implicated in many physiological and pathophysiological processes associated with purinergic signaling, ...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.
External linksNat Struct Mol Biol / PubMed:32231289
MethodsEM (single particle)
Resolution3.38 - 3.77 Å
Structure data

20964

6uzy

EMDB-20964, PDB-6uzy:
Cryo-EM structure of Xenopus tropicalis pannexin 1
Method: EM (single particle) / Resolution: 3.38 Å

21071

6v6d

EMDB-21071, PDB-6v6d:
Cryo-EM structure of human pannexin 1
Method: EM (single particle) / Resolution: 3.77 Å

Chemicals

ChemComp-6OU:
[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / phospholipid*YM

ChemComp-R16:
HEXADECANE / Hexadecane

Source
  • xenopus tropicalis (tropical clawed frog)
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / ion channel / pannexin 1

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