The cryo-EM structure of a pannexin 1 reveals unique motifs for ion selection and inhibition

Michalski, K., Syrjanen, J. L., Henze, E., Kumpf, J., Furukawa, H., Kawate, T. (February 2020) The cryo-EM structure of a pannexin 1 reveals unique motifs for ion selection and inhibition. Elife, 9. ISSN 2050-084x

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Abstract

Pannexins are large-pore forming channels responsible for ATP release under a variety of physiological and pathological conditions. Although predicted to share similar membrane topology with other large-pore forming proteins such as connexins, innexins, and LRRC8, pannexins have minimal sequence similarity to these protein families. Here, we present the cryo-EM structure of a frog pannexin 1 (Panx1) channel at 3.0 A. We find that Panx1 protomers harbor four transmembrane helices similar in arrangement to other large-pore forming proteins but assemble as a heptameric channel with a unique constriction formed by Trp74 in the first extracellular loop. Mutating Trp74 or the nearby Arg75 disrupt ion selectivity whereas altering residues in the hydrophobic groove formed by the two extracellular loops abrogates channel inhibition by carbenoxolone. Our structural and functional study establishes the extracellular loops as important structural motifs for ion selectivity and channel inhibition in Panx1.

Item Type: Paper
Subjects: Investigative techniques and equipment > microscopy > Cryo-electron microscopy
organism description > animal > Frog
Investigative techniques and equipment
organism description > animal
organism description > animal > mammal > primates > hominids
organism description > animal > mammal > primates > hominids > human
organism description > animal > mammal
Investigative techniques and equipment > microscopy
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
organism description > animal > mammal > primates
structural biology
organism description > animal > Frog > xenopus
CSHL Authors:
Communities: CSHL labs > Furukawa lab
Depositing User: Adrian Gomez
Date: 12 February 2020
Date Deposited: 14 Feb 2020 19:03
Last Modified: 01 Feb 2024 16:18
PMCID: PMC7108861
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39054

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