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The structural basis for Z α1-antitrypsin polymerization in the liver.
Faull, Sarah V; Elliston, Emma L K; Gooptu, Bibek; Jagger, Alistair M; Aldobiyan, Ibrahim; Redzej, Adam; Badaoui, Magd; Heyer-Chauhan, Nina; Rashid, S Tamir; Reynolds, Gary M; Adams, David H; Miranda, Elena; Orlova, Elena V; Irving, James A; Lomas, David A.
Afiliación
  • Faull SV; UCL Respiratory, University College London, 5 University Street, London WC1E 6JF, UK.
  • Elliston ELK; UCL Respiratory, University College London, 5 University Street, London WC1E 6JF, UK.
  • Gooptu B; Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BN, UK.
  • Jagger AM; Leicester Institute of Structural and Chemical Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 7HB, UK.
  • Aldobiyan I; National Institute for Health Research (NIHR) Leicester BRC-Respiratory, Leicester, UK.
  • Redzej A; Institute of Structural and Molecular Biology, Birkbeck College, Malet Street, University of London, London WC1E 7HX, UK.
  • Badaoui M; UCL Respiratory, University College London, 5 University Street, London WC1E 6JF, UK.
  • Heyer-Chauhan N; Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BN, UK.
  • Rashid ST; UCL Respiratory, University College London, 5 University Street, London WC1E 6JF, UK.
  • Reynolds GM; Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BN, UK.
  • Adams DH; Institute of Structural and Molecular Biology, Birkbeck College, Malet Street, University of London, London WC1E 7HX, UK.
  • Miranda E; UCL Respiratory, University College London, 5 University Street, London WC1E 6JF, UK.
  • Orlova EV; UCL Respiratory, University College London, 5 University Street, London WC1E 6JF, UK.
  • Irving JA; Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BN, UK.
  • Lomas DA; Centre for Stem Cells and Regenerative Medicine and Institute for Liver Studies, King's College London, London WC2R 2LS, UK.
Sci Adv ; 6(43)2020 10.
Article en En | MEDLINE | ID: mdl-33087346
ABSTRACT
The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. α1-Antitrypsin deficiency is the archetypal serpinopathy and results from the formation and deposition of mutant forms of α1-antitrypsin as "polymer" chains in liver tissue. No detailed structural analysis has been performed of this material. Moreover, there is little information on the relevance of well-studied artificially induced polymers to these disease-associated molecules. We have isolated polymers from the liver tissue of Z α1-antitrypsin homozygotes (E342K) who have undergone transplantation, labeled them using a Fab fragment, and performed single-particle analysis of negative-stain electron micrographs. The data show structural equivalence between heat-induced and ex vivo polymers and that the intersubunit linkage is best explained by a carboxyl-terminal domain swap between molecules of α1-antitrypsin.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Adv Año: 2020 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Adv Año: 2020 Tipo del documento: Article País de afiliación: Reino Unido