Site-directed allostery perturbation to probe the negative regulation of hypoxia inducible factor-1α.

ABSTRACT: The interaction between the intrinsically disordered transcription factor HIF-1α and the coactivator proteins p300/CBP is essential in the fast response to low oxygenation. The negative feedback regulator, CITED2, switches off the hypoxic response through a very efficient irreversible mechanism. The negative cooperativity with HIF-1α relies on the formation of a ternary intermediate that leads to allosteric structural changes in p300/CBP, in which the cooperative folding/binding of the CITED2 sequence motifs plays a key role. Understanding the contribution of a binding motif to the structural changes in relation to competition efficiency provides invaluable insights into the molecular mechanism. Our strategy is to site-directedly perturb the p300-CITED2 complex's structure without signific

SUBMITTER: Petrovicz VL 

PROVIDER: S-EPMC11289882 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature