Combined prediction and design reveals the target recognition mechanism of an intrinsically disordered protein interaction domain.

ABSTRACT: An increasing number of protein interaction domains and their targets are being found to be intrinsically disordered proteins (IDPs). The corresponding target recognition mechanisms are mostly elusive because of challenges in performing detailed structural analysis of highly dynamic IDP-IDP complexes. Here, we show that by combining recently developed computational approaches with experiments, the structure of the complex between the intrinsically disordered C-terminal domain (CTD) of protein 4.1G and its target IDP region in NuMA can be dissected at high resolution. First, we carry out systematic mutational scanning using dihydrofolate reductase-based protein complementarity analysis to identify essential interaction regions and key residues. The results are found to be highly consistent

SUBMITTER: Hu X 

PROVIDER: S-EPMC10523638 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature