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Structures of wild-type and selected CMT1X mutant connexin 32 gap junction channels and hemichannels.
Qi, Chao; Lavriha, Pia; Bayraktar, Erva; Vaithia, Anand; Schuster, Dina; Pannella, Micaela; Sala, Valentina; Picotti, Paola; Bortolozzi, Mario; Korkhov, Volodymyr M.
Afiliación
  • Qi C; Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Lavriha P; Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.
  • Bayraktar E; Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Vaithia A; Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.
  • Schuster D; Veneto Institute of Molecular Medicine (VIMM), Padua, Italy.
  • Pannella M; Department of Physics and Astronomy "G. Galilei", University of Padua, Padua, Italy.
  • Sala V; Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Picotti P; Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.
  • Bortolozzi M; Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Korkhov VM; Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.
Sci Adv ; 9(35): eadh4890, 2023 09.
Article en En | MEDLINE | ID: mdl-37647412
In myelinating Schwann cells, connection between myelin layers is mediated by gap junction channels (GJCs) formed by docked connexin 32 (Cx32) hemichannels (HCs). Mutations in Cx32 cause the X-linked Charcot-Marie-Tooth disease (CMT1X), a degenerative neuropathy without a cure. A molecular link between Cx32 dysfunction and CMT1X pathogenesis is still missing. Here, we describe the high-resolution cryo-electron cryo-myography (cryo-EM) structures of the Cx32 GJC and HC, along with two CMT1X-linked mutants, W3S and R22G. While the structures of wild-type and mutant GJCs are virtually identical, the HCs show a major difference: In the W3S and R22G mutant HCs, the amino-terminal gating helix partially occludes the pore, consistent with a diminished HC activity. Our results suggest that HC dysfunction may be involved in the pathogenesis of CMT1X.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Charcot-Marie-Tooth / Conexinas Límite: Humans Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Charcot-Marie-Tooth / Conexinas Límite: Humans Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos