Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal

Detalhes bibliográficos
Autor(a) principal: Morgado, Isabel
Data de Publicação: 2008
Outros Autores: Melo, Eduardo P., Lundberg, Erik, Estrela, Nídia L., Sauer-Eriksson, A. Elisabeth, Power, Deborah
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/5419
Resumo: Transthyretin (TTR) transports thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3) in the blood of vertebrates. TH-binding sites are highly conserved in vertebrate TTR however, piscine TTR has a longer N-terminus which is thought to influence TH-binding affinity and may influence TTR stability. We produced recombinant wild-type sea bream TTR (sbTTRWT) plus two mutants in which six (sbTTRM6) and twelve (sbTTRM12) N-terminal residues were removed. Ligandbinding studies revealed similar affinities for T3 (Kd=10.6±1.7nM) and T4 (Kd=9.8±0.97nM) binding to sbTTRWT. Affinity for THs was unaltered in sbTTRM12 but sbTTRM6 had poorer affinity for T4 (Kd=252.3±15.8nM) implying that some residues in the N-terminus can influence T4 binding. sbTTRM6 inhibited acid-mediated fibril formation in vitro as shown by fluorometric measurements using thioflavine-T.In contrast, fibril formation by sbTTRM12 was significant, probably due to decreased stability of the tetramer. Such studies also suggested that sbTTRWT is more resistant to fibril formation than human TTR.
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spelling Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminalAmyloid fibrilsRecombinant proteinLigand binding characteristicsTransthyretinTTR tetramer stabilityTransthyretin (TTR) transports thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3) in the blood of vertebrates. TH-binding sites are highly conserved in vertebrate TTR however, piscine TTR has a longer N-terminus which is thought to influence TH-binding affinity and may influence TTR stability. We produced recombinant wild-type sea bream TTR (sbTTRWT) plus two mutants in which six (sbTTRM6) and twelve (sbTTRM12) N-terminal residues were removed. Ligandbinding studies revealed similar affinities for T3 (Kd=10.6±1.7nM) and T4 (Kd=9.8±0.97nM) binding to sbTTRWT. Affinity for THs was unaltered in sbTTRM12 but sbTTRM6 had poorer affinity for T4 (Kd=252.3±15.8nM) implying that some residues in the N-terminus can influence T4 binding. sbTTRM6 inhibited acid-mediated fibril formation in vitro as shown by fluorometric measurements using thioflavine-T.In contrast, fibril formation by sbTTRM12 was significant, probably due to decreased stability of the tetramer. Such studies also suggested that sbTTRWT is more resistant to fibril formation than human TTR.ElsevierSapientiaMorgado, IsabelMelo, Eduardo P.Lundberg, ErikEstrela, Nídia L.Sauer-Eriksson, A. ElisabethPower, Deborah2014-10-23T09:34:13Z20082008-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/5419engIsabel Morgado, Eduardo P. Melo, Erik Lundberg, N´ıdia L. Estrela, A. Elisabeth Sauer-Eriksson, Deborah M. Power, "Hormone affinity and fibril formation of piscine transthyretin The role of the N-terminal" in Molecular and Cellular Endocrinology 295, 1-2 (2008) 48.0303-7207AUT: ELU70091; DPO00386;http://dx.doi.org/10.1016/j.mce.2008.06.010info: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:RCAAP2023-07-24T10:16:39Zoai:sapientia.ualg.pt:10400.1/5419Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:58:29.346018Repositório 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 Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
title Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
spellingShingle Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
Morgado, Isabel
Amyloid fibrils
Recombinant protein
Ligand binding characteristics
Transthyretin
TTR tetramer stability
title_short Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
title_full Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
title_fullStr Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
title_full_unstemmed Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
title_sort Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
author Morgado, Isabel
author_facet Morgado, Isabel
Melo, Eduardo P.
Lundberg, Erik
Estrela, Nídia L.
Sauer-Eriksson, A. Elisabeth
Power, Deborah
author_role author
author2 Melo, Eduardo P.
Lundberg, Erik
Estrela, Nídia L.
Sauer-Eriksson, A. Elisabeth
Power, Deborah
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv Morgado, Isabel
Melo, Eduardo P.
Lundberg, Erik
Estrela, Nídia L.
Sauer-Eriksson, A. Elisabeth
Power, Deborah
dc.subject.por.fl_str_mv Amyloid fibrils
Recombinant protein
Ligand binding characteristics
Transthyretin
TTR tetramer stability
topic Amyloid fibrils
Recombinant protein
Ligand binding characteristics
Transthyretin
TTR tetramer stability
description Transthyretin (TTR) transports thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3) in the blood of vertebrates. TH-binding sites are highly conserved in vertebrate TTR however, piscine TTR has a longer N-terminus which is thought to influence TH-binding affinity and may influence TTR stability. We produced recombinant wild-type sea bream TTR (sbTTRWT) plus two mutants in which six (sbTTRM6) and twelve (sbTTRM12) N-terminal residues were removed. Ligandbinding studies revealed similar affinities for T3 (Kd=10.6±1.7nM) and T4 (Kd=9.8±0.97nM) binding to sbTTRWT. Affinity for THs was unaltered in sbTTRM12 but sbTTRM6 had poorer affinity for T4 (Kd=252.3±15.8nM) implying that some residues in the N-terminus can influence T4 binding. sbTTRM6 inhibited acid-mediated fibril formation in vitro as shown by fluorometric measurements using thioflavine-T.In contrast, fibril formation by sbTTRM12 was significant, probably due to decreased stability of the tetramer. Such studies also suggested that sbTTRWT is more resistant to fibril formation than human TTR.
publishDate 2008
dc.date.none.fl_str_mv 2008
2008-01-01T00:00:00Z
2014-10-23T09:34:13Z
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/10400.1/5419
url http://hdl.handle.net/10400.1/5419
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Isabel Morgado, Eduardo P. Melo, Erik Lundberg, N´ıdia L. Estrela, A. Elisabeth Sauer-Eriksson, Deborah M. Power, "Hormone affinity and fibril formation of piscine transthyretin The role of the N-terminal" in Molecular and Cellular Endocrinology 295, 1-2 (2008) 48.
0303-7207
AUT: ELU70091; DPO00386;
http://dx.doi.org/10.1016/j.mce.2008.06.010
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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