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Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP

Rittinger, Katrin, Walker, Philip A., Eccleston, John F., Nurmahomed, Kurshid, Owen, Darerca, Laue, Ernest, Gamblin, Steven J., Smerdon, Stephen J.·1997·Nature
DOI 10.1038/41805
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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.

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Research works printed but not linked: 28

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Metadata

Authors
Rittinger, K., Walker, P. A., Eccleston, J. F., Nurmahomed, K., Owen, D., Laue, E., Gamblin, S. J., & Smerdon, S. J.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
1997-08-14
Volume
388
Issue
6643
Pages
693-697
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/41805
Cited by
227
References
1
Language
en
Licence

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CoChat. (2026). Citation check: Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP. https://app.cochat.ai/papers/10.1038/41805
The paper
Rittinger, K., Walker, P. A., Eccleston, J. F., Nurmahomed, K., Owen, D., Laue, E., Gamblin, S. J., & Smerdon, S. J. (1997). Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP. Nature. https://doi.org/10.1038/41805