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

Autor: Myers JB; Department of Chemistry, Portland State University, Portland, OR, USA., Haddad BG; Department of Chemistry, Portland State University, Portland, OR, USA., O'Neill SE; Department of Chemistry, Portland State University, Portland, OR, USA., Chorev DS; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK., Yoshioka CC; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA., Robinson CV; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK., Zuckerman DM; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA., Reichow SL; Department of Chemistry, Portland State University, Portland, OR, USA. reichow@pdx.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2018 Dec; Vol. 564 (7736), pp. 372-377. Date of Electronic Publication: 2018 Dec 12.
DOI: 10.1038/s41586-018-0786-7
Abstrakt: 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.
Databáze: MEDLINE
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