Catalytic site mutations confer multiple states of G protein activation.

ABSTRACT: Heterotrimeric guanine nucleotide-binding proteins (G proteins) that function as molecular switches for cellular growth and metabolism are activated by GTP and inactivated by GTP hydrolysis. In uveal melanoma, a conserved glutamine residue critical for GTP hydrolysis in the G protein α subunit is often mutated in Gα_q or Gα₁₁ to either leucine or proline. In contrast, other glutamine mutations or mutations in other Gα subtypes are rare. To uncover the mechanism of the genetic selection and the functional role of this glutamine residue, we analyzed all possible substitutions of this residue in multiple Gα isoforms. Through cell-based measurements of activity, we showed that some mutants were further activated and inactivated by G protein-coupled receptors. Through bioch

SUBMITTER: Hewitt N 

PROVIDER: S-EPMC10021883 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature