Structure of an inactive conformation of GTP-bound RhoA GTPase.

ABSTRACT: By using ³¹P NMR, we present evidence that the Rho family GTPase RhoA, similar to Ras GTPases, exists in an equilibrium of conformations when bound to GTP. High-resolution crystal structures of RhoA bound to the GTP analog GMPPNP and to GDP show that they display a similar overall inactive conformation. In contrast to the previously reported crystal structures of GTP analog-bound forms of two RhoA dominantly active mutants (G14V and Q63L), GMPPNP-bound RhoA assumes an open conformation in the Switch I loop with a previously unseen interaction between the γ-phosphate and Pro36, instead of the canonical Thr37. Molecular dynamics simulations found that the oncogenic RhoA^G14V mutant displays a reduced flexibility in the Switch regions, consistent with a crystal structure

SUBMITTER: Lin Y 

PROVIDER: S-EPMC8178163 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature