Bivalent interaction through an intrinsically disordered linker promotes transcription activation complex assembly in Notch signaling.

ABSTRACT: The Notch signaling pathway regulates cellular differentiation by activating transcription through an unusual heterotrimeric complex comprising the Notch receptor's intracellular domain (NICD), the DNA-binding protein CSL, and the coactivator MAML. NICD has two binding sites for CSL, a short motif in the RAM region and an ankyrin domain (ANK), connected by an intrinsically disordered linker and which form a bivalent ternary complex with CSL and MAML. Although bivalency is required for maximal transcription activation, the energetic contributions of bivalency and heterotrimer formation within this essential complex are unknown. To elucidate the energetics of bivalency, we first determine the free energy of the CSL-ANK-MAML heterotrimer, using isothermal titration calorimetry and developing

SUBMITTER: Cook C 

PROVIDER: S-EPMC12318201 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature