Connexins -- Analysis, Cell interaction, Gap junctions (Cell biology), Cataract -- Genetic aspects
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.
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Myers, J. B., Haddad, B. G., O’Neill, S. E., Chorev, D. S., Yoshioka, C. C., Robinson, C. V., … Reichow, S. L. (2018). Structure of native lens connexin 46/50 intercellular channels by cryo-EM. Nature, 564(7736), 372–377. https://doi.org/10.1038/s41586-018-0786-7