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TitleStructure of native lens connexin 46/50 intercellular channels by cryo-EM.
Journal, issue, pagesNature, Vol. 564, Issue 7736, Page 372-377, Year 2018
Publish dateDec 12, 2018
AuthorsJanette B Myers / Bassam G Haddad / Susan E O'Neill / Dror S Chorev / Craig C Yoshioka / Carol V Robinson / Daniel M Zuckerman / Steve L Reichow /
PubMed AbstractGap junctions establish direct pathways for cell-to-cell communication through the assembly of twelve connexin subunits that form intercellular channels connecting neighbouring cells. Co-assembly of ...Gap junctions establish direct pathways for cell-to-cell communication through the assembly of twelve connexin subunits that form intercellular channels connecting neighbouring cells. Co-assembly of different connexin isoforms produces channels with unique properties and enables communication across cell types. Here we used single-particle cryo-electron microscopy to investigate the structural basis of connexin co-assembly in native lens gap junction channels composed of connexin 46 and connexin 50 (Cx46/50). We provide the first comparative analysis to connexin 26 (Cx26), which-together with computational studies-elucidates key energetic features governing gap junction permselectivity. Cx46/50 adopts an open-state conformation that is distinct from the Cx26 crystal structure, yet it appears to be stabilized by a conserved set of hydrophobic anchoring residues. 'Hot spots' of genetic mutations linked to hereditary cataract formation map to the core structural-functional elements identified in Cx46/50, suggesting explanations for many of the disease-causing effects.
External linksNature / PubMed:30542154 / PubMed Central
MethodsEM (single particle)
Resolution3.4 Å
Structure data

9116

6mhq

6mhy

EMDB-9116: CryoEM reconstruction of native lens connexin-46/50 at 3.4 angstrom resolution
PDB-6mhq: Structure of connexin-46 intercellular gap junction channel at 3.4 angstrom resolution by cryoEM
PDB-6mhy: Structure of connexin-50 intercellular gap junction channel at 3.4 angstrom resolution by cryoEM
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • ovis aries (sheep)
  • Sheep (sheep)
KeywordsMEMBRANE PROTEIN / ion channel / gap junction / cell communication / connexin

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