Structure of native lens connexin 46/50 intercellular channels by cryo-EM

Article

关键词: GAP-JUNCTION CHANNELS;    MOLECULAR-DYNAMICS SIMULATIONS;    PERMEATION PATHWAY;    SELECTIVE PERMEABILITY;    CHARGE SELECTIVITY;    VOLTAGE;    PROTEINS;    MECHANISM;    MODEL;    CX50;   

DOI  :  10.1038/s41586-018-0786-7

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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