Negative cooperativity regulates ligand activation of DIAPH1 and other diaphanous related formins.

ABSTRACT: DIAPH1 is a member of the family of Diaphanous Related Formins (DRFs) implicated in cell migration and cytokinesis. DRFs are maintained in an autoinhibited state by the intramolecular association between diaphanous inhibitory (DID) and diaphanous autoregulatory (DAD) domains. Actin polymerization requires the binding of activated RhoA to the GTPase binding domain (GBD) of DIAPH1 and the dissociation of DAD. In the presence of excess RhoA, actin polymerization is only partially activated. Using monomeric domain constructs of DIAPH1, the sequential binding affinities of RhoA and DAD to GBD-DID were characterized. Binding of RhoA and DAD were negatively cooperative requiring a 100-fold greater concentration of DAD to achieve saturation when RhoA binding site was occupied. The unimolecular arc

SUBMITTER: Theophall GG 

PROVIDER: S-EPMC12095592 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature