6v6m
From Proteopedia
Crystal structure of an inactive state of GMPPNP-bound RhoA
Structural highlights
Function[RHOA_HUMAN] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedBy using (31)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 gamma-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 of GDP-bound RhoA(G14V). 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. Structure of an inactive conformation of GTP-bound RhoA GTPase.,Lin Y, Lu S, Zhang J, Zheng Y Structure. 2021 Jan 12. pii: S0969-2126(20)30482-2. doi:, 10.1016/j.str.2020.12.015. PMID:33497604[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Small monomeric GTPase | Lin, Y | Zheng, Y | Gtpase | Hydrolase | Switch i | Switch ii
