The sequence-ensemble relationship in fuzzy protein complexes.
Proc Natl Acad Sci U S A
; 118(37)2021 09 14.
Article
em En
| MEDLINE
| ID: mdl-34504009
ABSTRACT
Intrinsically disordered proteins (IDPs) interact with globular proteins through a variety of mechanisms, resulting in the structurally heterogeneous ensembles known as fuzzy complexes. While there exists a reasonable comprehension on how IDP sequence determines the unbound IDP ensemble, little is known about what shapes the structural characteristics of IDPs bound to their targets. Using a statistical thermodynamic model, we show that the target-bound ensembles are determined by a simple code that combines the IDP sequence and the distribution of IDP-target interaction hotspots. These two parameters define the conformational space of target-bound IDPs and rationalize the observed structural heterogeneity of fuzzy complexes. The presented model successfully reproduces the dynamical signatures of target-bound IDPs from the NMR relaxation experiments as well as the changes of interaction affinity and the IDP helicity induced by mutations. The model explains how the target-bound IDP ensemble adapts to mutations in order to achieve an optimal balance between conformational freedom and interaction energy. Taken together, the presented sequence-ensemble relationship of fuzzy complexes explains the different manifestations of IDP disorder in folding-upon-binding processes.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
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Termodinâmica
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Dobramento de Proteína
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Proteínas Intrinsicamente Desordenadas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article