Different degrees of structural order in distinct regions of the transcriptional repressor HES-1

► The bHLH domain is marginally stable and folds upon dimerization. ► Binding to DNA promotes folding and stabilization of the bHLH domain. ► The Orange domain is a stable helical dimer. ► HES-1 recognizes dsDNA with high affinity but with low specificity. ► Order/disorder transitions may drive HES-1 homo- and hetero-dimerization.