Small Molecule-Induced Domain Swapping as a Mechanism for Controlling Protein Function and Assembly.

ABSTRACT: Domain swapping is the process by which identical proteins exchange reciprocal segments to generate dimers. Here we introduce induced domain swapping (INDOS) as a mechanism for regulating protein function. INDOS employs a modular design consisting of the fusion of two proteins: a recognition protein that binds a triggering molecule, and a target protein that undergoes a domain swap in response to binding of the triggering ligand. The recognition protein (FK506 binding protein) is inserted into functionally-inactivated point mutants of two target proteins (staphylococcal nuclease and ribose binding protein). Binding of FK506 to the FKBP domain causes the target domain to first unfold, then refold via domain swap. The inactivating mutations become 'swapped out' in the dimer, increasing nucle

SUBMITTER: Karchin JM 

PROVIDER: S-EPMC5347425 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature