6V6M

Crystal structure of an inactive state of GMPPNP-bound RhoA

Summary for 6V6M

• Entry DOI: 10.2210/pdb6v6m/pdb
• Related: 6V6U 6V6V
• Descriptor: Transforming protein RhoA, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: gtpase, switch i, switch ii, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 21301.23

Authors

Lin, Y.,Zheng, Y. (deposition date: 2019-12-05, release date: 2020-12-09, Last modification date: 2023-10-11)

Primary citation

Lin, Y.,Lu, S.,Zhang, J.,Zheng, Y.
Structure of an inactive conformation of GTP-bound RhoA GTPase.
Structure, 29:553-563.e5, 2021

PubMed Abstract: By using P 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 mutant displays a reduced flexibility in the Switch regions, consistent with a crystal structure of GDP-bound RhoA. Thus, GDP- and GTP-bound RhoA can present similar inactive conformations, and the molecular dynamics in the Switch regions are likely to have a role in RhoA activation.

PubMed: 33497604
DOI: 10.1016/j.str.2020.12.015

Experimental method

X-RAY DIFFRACTION (1.39 Å)