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TitleCryo-EM structure of human Cx31.3/GJC3 connexin hemichannel.
Journal, issue, pagesSci Adv, Vol. 6, Issue 35, Page eaba4996, Year 2020
Publish dateAug 28, 2020
AuthorsHyuk-Joon Lee / Hyeongseop Jeong / Jaekyung Hyun / Bumhan Ryu / Kunwoong Park / Hyun-Ho Lim / Jejoong Yoo / Jae-Sung Woo /
PubMed AbstractConnexin family proteins assemble into hexameric channels called hemichannels/connexons, which function as transmembrane channels or dock together to form gap junction intercellular channels (GJIChs). ...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.
External linksSci Adv / PubMed:32923625 / PubMed Central
MethodsEM (single particle)
Resolution2.34 - 2.63 Å
Structure data

0825

6l3t

EMDB-0825, PDB-6l3t:
Human Cx31.3/GJC3 connexin hemichannel in the absence of calcium
Method: EM (single particle) / Resolution: 2.34 Å

0826

6l3u

EMDB-0826, PDB-6l3u:
Human Cx31.3/GJC3 connexin hemichannel in the presence of calcium
Method: EM (single particle) / Resolution: 2.53 Å

0827

6l3v

EMDB-0827, PDB-6l3v:
The R15G mutant of human Cx31.3/GJC3 connexin hemichannel
Method: EM (single particle) / Resolution: 2.63 Å

Chemicals

ChemComp-LMN:
Lauryl Maltose Neopentyl Glycol / detergent*YM

ChemComp-HOH:
WATER / Water

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Gap junction / Hemichannel / Hexamer / ATP release

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