Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions.
Sci Adv
; 10(28): eadk6580, 2024 Jul 12.
Article
em En
| MEDLINE
| ID: mdl-38985864
ABSTRACT
The functional properties of RNA binding proteins (RBPs) require allosteric regulation through interdomain communication. Despite the importance of allostery to biological regulation, only a few studies have been conducted to describe the biophysical nature by which interdomain communication manifests in RBPs. Here, we show for hnRNP A1 that interdomain communication is vital for the unique stability of its amino-terminal domain, which consists of two RNA recognition motifs (RRMs). These RRMs exhibit drastically different stability under pressure. RRM2 unfolds as an individual domain but remains stable when appended to RRM1. Variants that disrupt interdomain communication between the tandem RRMs show a significant decrease in stability. Carrying these mutations over to the full-length protein for in vivo experiments revealed that the mutations affected the ability of the disordered carboxyl-terminal domain to engage in protein-protein interactions and influenced the protein's RNA binding capacity. Collectively, this work reveals that thermodynamic coupling between the tandem RRMs of hnRNP A1 accounts for its allosteric regulatory functions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligação Proteica
/
Termodinâmica
/
RNA
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Motivo de Reconhecimento de RNA
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Ribonucleoproteína Nuclear Heterogênea A1
Limite:
Humans
Idioma:
En
Revista:
Sci Adv
/
Sci. Adv
/
Science advances
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos