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Updated: May 1, 2026

Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
Published on: January 5, 2024
Protein dynamics of the HIF-2α PAS-B domain upon heterodimerization and ligand binding
Matteo Masetti1, Federico Falchi1, Maurizio Recanatini1
1Department of Pharmacy and Biotechnology, Alma Mater Studiorum-Università di Bologna, Bologna, Italy.
Abstract:
Hypoxia-Inducible Factor (HIF) transcription factors are heterodimeric proteins involved in the regulation of oxygen homeostatis. Their upregulation has been related to several tumors with a remarkably poor clinical outcome. The recent discovery of a druggable cavity in the HIF-2α PAS-B domain has opened an unprecedented opportunity for targeting the HIF-2α transcription factor in view of pharmaceutical strategies. Coincidentally, a novel compound able to selectively disrupt the HIF heterodimerization with a submicromolar activity has been reported. In this work, we investigated the molecular mechanisms responsible for the inhibition by comparing the dynamical features of the HIF-2α PAS-B monomer and the HIF-2α PAS-B/HIF-1β PAS-B complex, in the ligand-bound and -unbound states. Plain and biased Molecular Dynamics were used to characterize the differential conformational changes both structurally and energetically.
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