6MHQ

Structure of connexin-46 intercellular gap junction channel at 3.4 angstrom resolution by cryoEM

Summary for 6MHQ

• Entry DOI: 10.2210/pdb6mhq/pdb
• EMDB information: 9116
• Descriptor: Gap junction alpha-3 protein, connexin-46 (1 entity in total)
• Functional Keywords: ion channel, gap junction, cell communication, connexin, membrane protein
• Biological source: Ovis aries (Sheep)
• Total number of polymer chains: 12
• Total formula weight: 455622.19

Authors

Myers, J.B.,Reichow, S.L. (deposition date: 2018-09-18, release date: 2018-12-12, Last modification date: 2019-12-18)

Primary citation

Myers, J.B.,Haddad, B.G.,O'Neill, S.E.,Chorev, D.S.,Yoshioka, C.C.,Robinson, C.V.,Zuckerman, D.M.,Reichow, S.L.
Structure of native lens connexin 46/50 intercellular channels by cryo-EM.
Nature, 564:372-377, 2018

PubMed Abstract: 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.

PubMed: 30542154
DOI: 10.1038/s41586-018-0786-7

Experimental method

ELECTRON MICROSCOPY (3.4 Å)