Self-Effected Allosteric Coupling and Cooperativity in Hypoxic Response Regulation with Disordered Proteins.
J Phys Chem Lett
; 13(39): 9201-9209, 2022 Oct 06.
Article
em En
| MEDLINE
| ID: mdl-36170455
ABSTRACT
Hypersensitive regulation of cellular hypoxic response relies on cooperative displacement of one disordered protein (HIF-1α) by another disordered protein (CITED2) from the target in a negative feedback loop. Considering the weak intramolecule coupling in disordered proteins, the molecular mechanism of high cooperativity in the molecular displacement event remains elusive. Herein, we show that disordered proteins utilize a "self-effected allostery" mechanism to achieve high binding cooperativity. Different from the conventional allostery mechanisms shown by many structured or disordered proteins, this mechanism utilizes one part of the disordered protein as the effector to trigger the allosteric coupling and enhance the binding of the remaining part of the same disordered protein, contributing to high cooperativity of the displacement event. The conserved charge motif of CITED2 is the key determinant of the molecular displacement event by serving as the effector of allosteric coupling. Such self-effected allostery provides an efficient strategy to achieve high cooperativity in the molecular events involving disordered proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Transativadores
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Phys Chem Lett
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China