Multivalency enables unidirectional switch-like competition between intrinsically disordered proteins

• DOI: 10.1073/pnas.2117338119
• Publication Date: 2022-01-10T21:26:09Z
• Authors: Rebecca B. Berlow; H. Jane Dyson; Peter E. Wright
• Keywords: Intrinsically Disordered Proteins; CREB-binding protein; Transcription

Significance Intrinsically disordered proteins must frequently compete for binding to shared interaction hubs perform their cellular functions. Here, we describe the mechanism by which two that regulate transcriptional response hypoxia folded TAZ1 domain of coactivators CBP and p300. CITED2, a negative feedback regulator HIF-1α, displaces HIF-1α from in unidirectional, switch-like manner. Efficient competition is highly dependent on flexibility multivalency CITED2 activation domains. Differences strength coupling motifs are key determinants unidirectionality underscore role regulation processes proteins.