Tryptophan mutations in G3BP1 tune the stability of a cellular signaling hub by weakening transient interactions with Caprin1 and USP10.

ABSTRACT: Intrinsically disordered proteins (IDPs) often coordinate transient interactions with multiple proteins to mediate complex signals within large protein networks. Among these, the IDP hub protein G3BP1 can form complexes with cytoplasmic phosphoprotein Caprin1 and ubiquitin peptidase USP10; the resulting control of USP10 activity contributes to a pathogenic virulence system that targets endocytic recycling of the ion channel CFTR. However, while the identities of protein interactors are known for many IDP hub proteins, the relationship between pairwise affinities and the extent of protein recruitment and activity is not well understood. Here, we describe in vitro analysis of these G3BP1 affinities and show tryptophan substitutions of specific G3BP1 residues reduce its affinity for both USP1

SUBMITTER: Sheehan CT 

PROVIDER: S-EPMC9723946 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature