Homodimerization of the PAS-B domains of hypoxia-inducible factors.

ABSTRACT: The Per-Arnt-Sim (PAS) domains of hypoxia-inducible transcription factors (HIF) mediate heterodimer formation between the HIF-α forms that are induced in the event of cellular hypoxia and the constitutive HIF-β variants. Previous efforts toward structural characterization of the HIF-1α PAS domains were limited by protein stability. Using homology modeling based on the published crystal structure of the PAS-B domain of the homologous protein HIF-2α in complex with the partner HIF-β (also known as ARNT), we have identified a variant of HIF-1α with improved solubility, monodispersity, and stability. Purified solutions of the PAS-B domains of HIF-1α and HIF-2α differ in their propensity for homodimer formation. In an attempt to understand the structural basis for this difference, and to docume

SUBMITTER: Zhu J 

PROVIDER: S-EPMC3376167 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature