Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin
Autor(a) principal: | |
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Data de Publicação: | 2000 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/5234 https://doi.org/10.1016/S0301-4622(00)00199-X |
Resumo: | Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant hereditary type of amyloidosis involving amino acid substitutions in transthyretin (TTR). V30M-TTR is the most frequent variant, and L55P-TTR is the variant associated with the most aggressive form of FAP. The thermal stability of the wild-type, V30M-TTR, L55P-TTR and a non-amyloidogenic variant, T119M-TTR, was studied by high-sensitivity differential scanning calorimetry (DSC). The thermal unfolding of TTR is a spontaneous reversible process involving a highly co-operative transition between folded tetramers and unfolded monomers. All variants of transthyretin are very stable to the thermal unfolding that occurs at very high temperatures, most probably because of their oligomeric structure. The data presented in this work indicated that for the homotetrameric form of the wild-type TTR and its variants, the order of stability is as follows: wild-type TTRT119M-TTR>L55P-TTR>V30M-TTR, which does not correlate with their known amyloidogenic potential. |
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Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretinTransthyretinFamilial amyloidotic polyneuropathyDifferential scanning calorimetryThermal stabilityFamilial amyloidotic polyneuropathy (FAP) is an autosomal dominant hereditary type of amyloidosis involving amino acid substitutions in transthyretin (TTR). V30M-TTR is the most frequent variant, and L55P-TTR is the variant associated with the most aggressive form of FAP. The thermal stability of the wild-type, V30M-TTR, L55P-TTR and a non-amyloidogenic variant, T119M-TTR, was studied by high-sensitivity differential scanning calorimetry (DSC). The thermal unfolding of TTR is a spontaneous reversible process involving a highly co-operative transition between folded tetramers and unfolded monomers. All variants of transthyretin are very stable to the thermal unfolding that occurs at very high temperatures, most probably because of their oligomeric structure. The data presented in this work indicated that for the homotetrameric form of the wild-type TTR and its variants, the order of stability is as follows: wild-type TTRT119M-TTR>L55P-TTR>V30M-TTR, which does not correlate with their known amyloidogenic potential.http://www.sciencedirect.com/science/article/B6TFB-41NK91T-5/1/472cf0fa1a8c059202a368bff37867202000info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5234http://hdl.handle.net/10316/5234https://doi.org/10.1016/S0301-4622(00)00199-XengBiophysical Chemistry. 88:1-3 (2000) 61-67Shnyrov, Valery L.Villar, EnriqueZhadan, Galina G.Sanchez-Ruiz, Jose M.Quintas, AlexandreSaraiva, Maria João M.Brito, Rui M. M.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2020-11-06T16:59:47Zoai:estudogeral.uc.pt:10316/5234Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:01:36.594017Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin |
title |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin |
spellingShingle |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin Shnyrov, Valery L. Transthyretin Familial amyloidotic polyneuropathy Differential scanning calorimetry Thermal stability |
title_short |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin |
title_full |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin |
title_fullStr |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin |
title_full_unstemmed |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin |
title_sort |
Comparative calorimetric study of non-amyloidogenic and amyloidogenic variants of the homotetrameric protein transthyretin |
author |
Shnyrov, Valery L. |
author_facet |
Shnyrov, Valery L. Villar, Enrique Zhadan, Galina G. Sanchez-Ruiz, Jose M. Quintas, Alexandre Saraiva, Maria João M. Brito, Rui M. M. |
author_role |
author |
author2 |
Villar, Enrique Zhadan, Galina G. Sanchez-Ruiz, Jose M. Quintas, Alexandre Saraiva, Maria João M. Brito, Rui M. M. |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Shnyrov, Valery L. Villar, Enrique Zhadan, Galina G. Sanchez-Ruiz, Jose M. Quintas, Alexandre Saraiva, Maria João M. Brito, Rui M. M. |
dc.subject.por.fl_str_mv |
Transthyretin Familial amyloidotic polyneuropathy Differential scanning calorimetry Thermal stability |
topic |
Transthyretin Familial amyloidotic polyneuropathy Differential scanning calorimetry Thermal stability |
description |
Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant hereditary type of amyloidosis involving amino acid substitutions in transthyretin (TTR). V30M-TTR is the most frequent variant, and L55P-TTR is the variant associated with the most aggressive form of FAP. The thermal stability of the wild-type, V30M-TTR, L55P-TTR and a non-amyloidogenic variant, T119M-TTR, was studied by high-sensitivity differential scanning calorimetry (DSC). The thermal unfolding of TTR is a spontaneous reversible process involving a highly co-operative transition between folded tetramers and unfolded monomers. All variants of transthyretin are very stable to the thermal unfolding that occurs at very high temperatures, most probably because of their oligomeric structure. The data presented in this work indicated that for the homotetrameric form of the wild-type TTR and its variants, the order of stability is as follows: wild-type TTRT119M-TTR>L55P-TTR>V30M-TTR, which does not correlate with their known amyloidogenic potential. |
publishDate |
2000 |
dc.date.none.fl_str_mv |
2000 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/5234 http://hdl.handle.net/10316/5234 https://doi.org/10.1016/S0301-4622(00)00199-X |
url |
http://hdl.handle.net/10316/5234 https://doi.org/10.1016/S0301-4622(00)00199-X |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biophysical Chemistry. 88:1-3 (2000) 61-67 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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