G Proteins

Abstract

The G proteins, or GTP‐binding proteins, can be classified into three major groups: the large mammalian Gαβγ heterotrimers, the small Ras and Ras‐like GTPases, and the intermediate‐sized GTPases such as elongation factors Tu (EF1A) and G (EF2). All G proteins function as molecular switches controlled by a GTPase cycle, shuttling between an active GTP–Mg2+‐bound form (the ‘on’ state) and an inactive GDP–Mg2+ complex (the ‘off’ state).

Keywords: heterotrimeric GTP‐binding proteins; Ras‐like proteins; elongation factors; molecular switch; signal transduction

Figure 1.

The GTPase cycle for elongation factor Tu (EF1A). The switch I and switch II regions of EF‐Tu are in yellow and orange, respectively. EF‐Tu is depicted in blue ribbons, EF‐Ts in green with its N‐terminal helix close to the empty guanine nucleotide‐binding pocket of EF‐Tu. The switch I region of EF‐Tu in the EF‐Tu–EF‐Ts complex is disordered and therefore not depicted. tRNA is shown as ball‐and‐stick model.

Figure 2.

Relative orientation of the switch II helix (orange) of inactive Gαi–GDP–Gβγ (a) and active Gαs–GTP in complex with adenylyl cyclase (b). Colours are as follows: Gβ (a) and adenylyl cyclase (b) are shown in green, Gγ is in yellow and Gα in blue.

Figure 3.

Stabilization of the transition state of the GTP hydrolysis reaction by a glutamine and an arginine residue, as visualized by X‐ray crystallographic analysis of the Gαi complex with GDP–Mg2+ and AlF4.

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References

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Further Reading

Aktories K (1997) Rho proteins: targets for bacterial toxins. Trends in Microbiology 5: 282–287.

Bourne HR (1997) The arginine finger strikes again. Nature 389: 673–674.

Geyer M and Wittinghofer A (1997) GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras‐related GTP‐binding proteins. Current Opinion in Structural Biology 7: 786–792.

Hamm HE (1998) The many faces of G protein signalling. Journal of Biological Chemistry 273: 669–672.

Hilgenfeld R (1995) How do the GTPases really work? Nature Structural Biology 2: 3–6.

Hilgenfeld R, Mesters F and Hogg T (2000) Insights into the GTPase mechanism of EF‐Tu from structural studies. In Garrett RA, Douthwaite SR et al. (eds) The Ribosome: Structure, Function, Antibiotics and Cellular Interactions, pp 347–357. Washington DC: ASM Press.

Sprang SR (1997) G protein mechanisms: insights from structural analysis. Annual Review of Biochemistry 66: 639–678.

Wilson KS and Noller HF (1998) Molecular movement inside the translational engine. Cell 92: 337–349.

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Mesters, Jeroen R, Hogg, Tanis, and Hilgenfeld, Rolf(Apr 2001) G Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000657]