Influence of an Intrinsically Disordered Region on Protein Domains Revealed by NMR-Based Electrostatic Potential Measurements.
J Am Chem Soc
; 146(22): 14922-14926, 2024 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-38771003
ABSTRACT
Many human proteins possess intrinsically disordered regions containing consecutive aspartate or glutamate residues ("D/E repeats"). Approximately half of them are DNA/RNA-binding proteins. In this study, using nuclear magnetic resonance (NMR) spectroscopy, we investigated the electrostatic properties of D/E repeats and their influence on folded domains within the same protein. Local electrostatic potentials were directly measured for the HMGB1 protein, its isolated D/E repeats, and DNA-binding domains by NMR. The data provide quantitative information about the electrostatic interactions between distinct segments of HMGB1. Due to the interactions between the D/E repeats and the DNA-binding domains, local electrostatic potentials of the DNA-binding domains within the full-length HMGB1 protein were largely negative despite the presence of many positively charged residues. Our NMR data on counterions and electrostatic potentials show that the D/E repeats and DNA have similar electrostatic properties and compete for the DNA-binding domains. The competition promotes dissociation of the protein-DNA complex and influences the molecular behavior of the HMGB1 protein. These effects may be general among the DNA/RNA-binding proteins with D/E repeats.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resonancia Magnética Nuclear Biomolecular
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Proteína HMGB1
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Electricidad Estática
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Dominios Proteicos
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos