Regulation of GTPase function by autophosphorylation.

ABSTRACT: A unifying feature of the RAS superfamily is a conserved GTPase cycle by which these proteins transition between active and inactive states. We demonstrate that autophosphorylation of some GTPases is an intrinsic regulatory mechanism that reduces nucleotide hydrolysis and enhances nucleotide exchange, altering the on/off switch that forms the basis for their signaling functions. Using X-ray crystallography, nuclear magnetic resonance spectroscopy, binding assays, and molecular dynamics on autophosphorylated mutants of H-RAS and K-RAS, we show that phosphoryl transfer from GTP requires dynamic movement of the switch II region and that autophosphorylation promotes nucleotide exchange by opening the active site and extracting the stabilizing Mg²⁺. Finally, we demonstrate that autop

SUBMITTER: Johnson CW 

PROVIDER: S-EPMC8986090 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature