The Thermodynamic Basis of the Fuzzy Interaction of an Intrinsically Disordered Protein.
Angew Chem Int Ed Engl
; 56(46): 14494-14497, 2017 11 13.
Article
em En
| MEDLINE
| ID: mdl-28914483
ABSTRACT
Many intrinsically disordered proteins (IDP) that fold upon binding retain conformational heterogeneity in IDP-target complexes. The thermodynamics of such fuzzy interactions is poorly understood. Herein we introduce a thermodynamic framework, based on analysis of ITC and CD spectroscopy data, that provides experimental descriptions of IDP association in terms of folding and binding contributions which can be predicted using sequence folding propensities and molecular modeling. We show how IDP can modulate the entropy and enthalpy by adapting their bound-state structural ensemble to achieve optimal binding. This is explained in terms of a free-energy landscape that provides the relationship between free-energy, sequence folding propensity, and disorder. The observed "fuzzy" behavior is possible because of IDP flexibility and also because backbone and side-chain interactions are, to some extent, energetically decoupled allowing IDP to minimize energetically unfavorable folding.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Termodinâmica
/
Lógica Fuzzy
/
Proteínas Intrinsicamente Desordenadas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Eslovênia