Structure of native lens connexin 46/50 intercellular channels by cryo-EM.
Nature
; 564(7736): 372-377, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30542154
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Conexinas
/
Microscopía por Crioelectrón
/
Cristalino
Límite:
Humans
Idioma:
En
Revista:
Nature
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos