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08.09.2020: Publication Alert - Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel

Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel

Abstract
Connexin family proteins assemble into hexameric channels called hemichannels/connexons, which function asConnexin family proteins assemble into hexameric channels called hemichannels/connexons, which function astransmembrane channels or dock together to form gap junction intercellular channels (GJIChs). We determinedthe cryo–electron microscopy structures of human connexin 31.3 (Cx31.3)/GJC3 hemichannels in the presenceand absence of calcium ions and with a hearing-loss mutation R15G at 2.3-, 2.5-, and 2.6-Å resolutions, respectively.Compared with available structures of GJICh in open conformation, Cx31.3 hemichannel shows substantial structuralchanges of highly conserved regions in the connexin family, including opening of calcium ion–bindingtunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminalhelices at the cytoplasmic entrance. We also found that the hemichannel has a pore with a diameter of ~8 Åand selectively transports chloride ions. Our study provides structural insights into the permeant selectivity ofCx31.3 hemichannel.


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