X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis

Transthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set of not yet fully characterized conformational changes, forms fibrillar aggregates that are the major protein component of amyloid deposits. More than 80 mutations associated with TTR amyloid deposition have been descri...

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Detalles Bibliográficos
Autores: Neto-Silva, Ricardo Miguel, Macedo-Ribeiro, Sandra, Pereira, Pedro José Barbosa, Coll, Miquel, Saraiva, Maria João, Damas, Ana Margarida
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2005
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/109026
Acceso en línea:http://hdl.handle.net/10261/109026
Access Level:acceso abierto
Palabra clave:familial amyloidotic polyneuropathy
Amyloids
transthyretin
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spelling X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesisNeto-Silva, Ricardo MiguelMacedo-Ribeiro, SandraPereira, Pedro José BarbosaColl, MiquelSaraiva, Maria JoãoDamas, Ana Margaridafamilial amyloidotic polyneuropathyAmyloidstransthyretinTransthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set of not yet fully characterized conformational changes, forms fibrillar aggregates that are the major protein component of amyloid deposits. More than 80 mutations associated with TTR amyloid deposition have been described in the literature. X-ray crystallography was used to elucidate the three-dimensional structure of two important TTR variants: TTR Y78F, an amyloidogenic protein, and TTR R104H, which is associated with a protective effect over the amyloidogenic V30M mutation. The structures of those two TTR variants have been determined in space group P21212 to 1.55 and 1.60 Å resolution, respectively, using molecular-replacement techniques. Detailed analysis of the protein model for TTR Y78F indicates a destabilization of the contacts between the α-helix and AB loop and the body of the molecule, intimately related to the amyloidogenic nature; contrastingly, in the TTR R104H variant new contacts involving the N-terminal region and His104 are clearly antagonists of amyloid formation. © 2005 International Union of Crystallography - all rights reserved.This work was funded by grants POCTI 71999/NSE/35735 and POCTI/NSE/44821/2002 from FCT (Fundaçao para a Ciencia e Tecnologia)Peer ReviewedBlackwell Publishing2014201420052014info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/109026reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1107/S0907444904034316info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1090262026-05-22T06:33:51Z
dc.title.none.fl_str_mv X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
title X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
spellingShingle X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
Neto-Silva, Ricardo Miguel
familial amyloidotic polyneuropathy
Amyloids
transthyretin
title_short X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
title_full X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
title_fullStr X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
title_full_unstemmed X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
title_sort X-ray crystallographic studies of two transthyretin variants: Further insights into amyloidogenesis
dc.creator.none.fl_str_mv Neto-Silva, Ricardo Miguel
Macedo-Ribeiro, Sandra
Pereira, Pedro José Barbosa
Coll, Miquel
Saraiva, Maria João
Damas, Ana Margarida
author Neto-Silva, Ricardo Miguel
author_facet Neto-Silva, Ricardo Miguel
Macedo-Ribeiro, Sandra
Pereira, Pedro José Barbosa
Coll, Miquel
Saraiva, Maria João
Damas, Ana Margarida
author_role author
author2 Macedo-Ribeiro, Sandra
Pereira, Pedro José Barbosa
Coll, Miquel
Saraiva, Maria João
Damas, Ana Margarida
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv familial amyloidotic polyneuropathy
Amyloids
transthyretin
topic familial amyloidotic polyneuropathy
Amyloids
transthyretin
description Transthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set of not yet fully characterized conformational changes, forms fibrillar aggregates that are the major protein component of amyloid deposits. More than 80 mutations associated with TTR amyloid deposition have been described in the literature. X-ray crystallography was used to elucidate the three-dimensional structure of two important TTR variants: TTR Y78F, an amyloidogenic protein, and TTR R104H, which is associated with a protective effect over the amyloidogenic V30M mutation. The structures of those two TTR variants have been determined in space group P21212 to 1.55 and 1.60 Å resolution, respectively, using molecular-replacement techniques. Detailed analysis of the protein model for TTR Y78F indicates a destabilization of the contacts between the α-helix and AB loop and the body of the molecule, intimately related to the amyloidogenic nature; contrastingly, in the TTR R104H variant new contacts involving the N-terminal region and His104 are clearly antagonists of amyloid formation. © 2005 International Union of Crystallography - all rights reserved.
publishDate 2005
dc.date.none.fl_str_mv 2005
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/109026
url http://hdl.handle.net/10261/109026
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1107/S0907444904034316
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Blackwell Publishing
publisher.none.fl_str_mv Blackwell Publishing
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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