RT Journal Article SR Electronic T1 Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaba4996 DO 10.1126/sciadv.aba4996 VO 6 IS 35 A1 Lee, Hyuk-Joon A1 Jeong, Hyeongseop A1 Hyun, Jaekyung A1 Ryu, Bumhan A1 Park, Kunwoong A1 Lim, Hyun-Ho A1 Yoo, Jejoong A1 Woo, Jae-Sung YR 2020 UL http://advances.sciencemag.org/content/6/35/eaba4996.abstract AB Connexin family proteins assemble into hexameric channels called hemichannels/connexons, which function as transmembrane channels or dock together to form gap junction intercellular channels (GJIChs). We determined the cryo–electron microscopy structures of human connexin 31.3 (Cx31.3)/GJC3 hemichannels in the presence and 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 structural changes of highly conserved regions in the connexin family, including opening of calcium ion–binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance. We also found that the hemichannel has a pore with a diameter of ~8 Å and selectively transports chloride ions. Our study provides structural insights into the permeant selectivity of Cx31.3 hemichannel.