4F38

Crystal structure of geranylgeranylated RhoA in complex with RhoGDI in its active GPPNHP-bound form

Summary for 4F38

• Entry DOI: 10.2210/pdb4f38/pdb
• Descriptor: Transforming protein RhoA, Rho GDP-dissociation inhibitor 1, GERAN-8-YL GERAN, ... (6 entities in total)
• Functional Keywords: rhoa, rhogdi, active gppnhp bound form, cell cycle-chaperone complex, cell cycle/chaperone
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 46218.89

Authors

Guo, Z.,Tnimov, Z.,Alexandrov, K. (deposition date: 2012-05-09, release date: 2012-05-23, Last modification date: 2024-10-16)

Primary citation

Tnimov, Z.,Guo, Z.,Gambin, Y.,Nguyen, U.T.,Wu, Y.W.,Abankwa, D.,Stigter, A.,Collins, B.M.,Waldmann, H.,Goody, R.S.,Alexandrov, K.
Quantitative Analysis of Prenylated RhoA Interaction with Its Chaperone, RhoGDI.
J.Biol.Chem., 287:26549-26562, 2012

PubMed Abstract: Small GTPases of the Rho family regulate cytoskeleton remodeling, cell polarity, and transcription, as well as the cell cycle, in eukaryotic cells. Membrane delivery and recycling of the Rho GTPases is mediated by Rho GDP dissociation inhibitor (RhoGDI), which forms a stable complex with prenylated Rho GTPases. We analyzed the interaction of RhoGDI with the active and inactive forms of prenylated and unprenylated RhoA. We demonstrate that RhoGDI binds the prenylated form of RhoA·GDP with unexpectedly high affinity (K(d) = 5 pm). The very long half-life of the complex is reduced 25-fold on RhoA activation, with a concomitant reduction in affinity (K(d) = 3 nm). The 2.8-Å structure of the RhoA·guanosine 5'-[β,γ-imido] triphosphate (GMPPNP)·RhoGDI complex demonstrated that complex formation forces the activated RhoA into a GDP-bound conformation in the absence of nucleotide hydrolysis. We demonstrate that membrane extraction of Rho GTPase by RhoGDI is a thermodynamically favored passive process that operates through a series of progressively tighter intermediates, much like the one that is mediated by RabGDI.

PubMed: 22628549
DOI: 10.1074/jbc.M112.371294

Experimental method

X-RAY DIFFRACTION (2.8 Å)