Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.typeArtigo de periódicopt_BR
dc.titleOn The Denaturation Mechanisms Of The Ligand Binding Domain Of Thyroid Hormone Receptors.pt_BR
dc.contributor.authorMartínez, Leandropt_BR
dc.contributor.authorSouza, Paulo C Tpt_BR
dc.contributor.authorGarcia, Waniuspt_BR
dc.contributor.authorBatista, Fernanda A Hpt_BR
dc.contributor.authorPortugal, Rodrigo Vpt_BR
dc.contributor.authorNascimento, Alessandro Spt_BR
dc.contributor.authorNakahira, Marcelpt_BR
dc.contributor.authorLima, Luis M T Rpt_BR
dc.contributor.authorPolikarpov, Igorpt_BR
dc.contributor.authorSkaf, Munir Spt_BR
unicamp.authorLeandro Martínez, Institute of Chemistry, State University of Campinas-UNICAMP, P.O. Box 6154, Campinas, SP, 13084-862, Brazil.pt_BR C T Souza,pt Garcia,pt A H Batista,pt V Portugal,pt S Nascimento,pt Nakahira,pt M T R Lima,pt Polikarpov,pt S Skaf,pt
dc.subjectAmino Acid Sequencept_BR
dc.subjectCircular Dichroismpt_BR
dc.subjectHydrophobic And Hydrophilic Interactionspt_BR
dc.subjectMolecular Dynamics Simulationpt_BR
dc.subjectMolecular Sequence Datapt_BR
dc.subjectProtein Denaturationpt_BR
dc.subjectProtein Foldingpt_BR
dc.subjectProtein Stabilitypt_BR
dc.subjectProtein Structure, Secondarypt_BR
dc.subjectProtein Structure, Tertiarypt_BR
dc.subjectSequence Alignmentpt_BR
dc.subjectSubstrate Specificitypt_BR
dc.subjectThyroid Hormone Receptors Alphapt_BR
dc.subjectThyroid Hormone Receptors Betapt_BR
dc.description.abstractThe ligand binding domain (LBD) of nuclear hormone receptors adopts a very compact, mostly alpha-helical structure that binds specific ligands with very high affinity. We use circular dichroism spectroscopy and high-temperature molecular dynamics simulations to investigate unfolding of the LBDs of thyroid hormone receptors (TRs). A molecular description of the denaturation mechanisms is obtained by molecular dynamics simulations of the TRalpha and TRbeta LBDs in the absence and in the presence of the natural ligand Triac. The simulations show that the thermal unfolding of the LBD starts with the loss of native contacts and secondary structure elements, while the structure remains essentially compact, resembling a molten globule state. This differs from most protein denaturation simulations reported to date and suggests that the folding mechanism may start with the hydrophobic collapse of the TR LBDs. Our results reveal that the stabilities of the LBDs of the TRalpha and TRbeta subtypes are affected to different degrees by the binding of the isoform selective ligand Triac and that ligand binding confers protection against thermal denaturation and unfolding in a subtype specific manner. Our simulations indicate two mechanisms by which the ligand stabilizes the LBD: (1) by enhancing the interactions between H8 and H11, and the interaction of the region between H1 and the Omega-loop with the core of the LBD, and (2) by shielding the hydrophobic H6 from hydration.en
dc.relation.ispartofThe Journal Of Physical Chemistry. Bpt_BR
dc.relation.ispartofabbreviationJ Phys Chem Bpt_BR
dc.identifier.citationThe Journal Of Physical Chemistry. B. v. 114, n. 3, p. 1529-40, 2010-Jan.pt_BR
dc.description.provenanceMade available in DSpace on 2015-11-27T13:18:39Z (GMT). No. of bitstreams: 1 pmed_20043653.pdf: 6611093 bytes, checksum: 4ab85eea616f749ae0d52f76d464176d (MD5) Previous issue date: 2010en
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
pmed_20043653.pdf6.46 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.