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.