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Structure of connexin-50 intercellular gap junction channel at 3.4 angstrom resolution by cryoEM
Structural highlights
FunctionCXA8_SHEEP One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Publication Abstract from PubMedGap 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. Structure of native lens connexin 46/50 intercellular channels by cryo-EM.,Myers JB, Haddad BG, O'Neill SE, Chorev DS, Yoshioka CC, Robinson CV, Zuckerman DM, Reichow SL Nature. 2018 Dec;564(7736):372-377. doi: 10.1038/s41586-018-0786-7. Epub 2018 Dec, 12. PMID:30542154[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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