Structure of the C-terminal guanine nucleotide exchange factor module of Trio in an autoinhibited conformation reveals its oncogenic potential.

ABSTRACT: The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gα_q/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gα_q/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility and gene transcription. This conserved signal transduction axis is crucial for tumor growth in uveal melanoma. Previous studies indicate that the GEF activity of the TrioC module is autoinhibited, with release of autoinhibition upon Gα_q/11 binding. Here, we determined the crystal structure of TrioC in its basal state and found that the pleckstrin homology (PH) domain interacts with the Dbl homology (DH) domain in a manner that occludes the Rho GT

SUBMITTER: Bandekar SJ 

PROVIDER: S-EPMC6519057 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature