1AM4

COMPLEX BETWEEN CDC42HS.GMPPNP AND P50 RHOGAP (H. SAPIENS)

Summary for 1AM4

• Entry DOI: 10.2210/pdb1am4/pdb
• Descriptor: P50-RHOGAP, CDC42HS, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: complex (gtpase-activating-gtp-binding), gtpase activation, complex (gtpase-activating-gtp-binding) complex, complex (gtpase-activating/gtp-binding)
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q07960; Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P60953
• Total number of polymer chains: 6
• Total formula weight: 128784.06

Authors

Rittinger, K.,Walker, P.,Gamblin, S.J.,Smerdon, S.J. (deposition date: 1997-06-22, release date: 1998-07-15, Last modification date: 2024-05-22)

Primary citation

Rittinger, K.,Walker, P.A.,Eccleston, J.F.,Nurmahomed, K.,Owen, D.,Laue, E.,Gamblin, S.J.,Smerdon, S.J.
Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP.
Nature, 388:693-697, 1997

PubMed Abstract: Small G proteins transduce signals from plasma-membrane receptors to control a wide range of cellular functions. These proteins are clustered into distinct families but all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of G proteins, which includes Cdc42Hs, activate effectors involved in the regulation of cytoskeleton formation, cell proliferation and the JNK signalling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GTPase-activating proteins (GAPs) that enhance the rate of GTP hydrolysis by up to 10(5) times. We report here the crystal structure of Cdc42Hs, with the non-hydrolysable GTP analogue GMPPNP, in complex with the GAP domain of p50rhoGAP at 2.7A resolution. In the complex Cdc42Hs interacts, mainly through its switch I and II regions, with a shallow pocket on rhoGAP which is lined with conserved residues. Arg 85 of rhoGAP interacts with the P-loop of Cdc42Hs, but from biochemical data and by analogy with the G-protein subunit G(i alpha1), we propose that it adopts a different conformation during the catalytic cycle which enables it to stabilize the transition state of the GTP-hydrolysis reaction.

PubMed: 9262406
DOI: 10.1038/41805

Experimental method

X-RAY DIFFRACTION (2.7 Å)