G Proteins


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.



Abel K, Yoder MD, Hilgenfeld R and Jurnak F (1996) An α to β conformational switch in EF‐Tu. Structure 4: 1153–1159.

Berchtold H, Reshetnikova L, Reiser COA, Schirmer NK, Sprinzl M and Hilgenfeld R (1993) Crystal structure of active elongation factor Tu reveals major domain rearrangements. Nature 365: 126–132.

Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG and Sprang SR (1994) Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis. Science 265: 1405–1412.

Nassar N, Horn G, Herrmann C, Scherer A, McCormick F and Wittinghofer A (1995) The 2.2 Å crystal structure of the Ras‐binding domain of the serine/threonine kinase c‐Raf1 in complex with RaplA and a GTP analogue. Nature 375: 554–560.

Nissen P, Kjeldgaard M, Thirup S et al. (1995) Crystal structure of the ternary complex of Phe‐tRNAPhe, EF‐Tu and a GTP analog. Science 270: 1464–1472.

Scheffzek K, Ahmadian MR, Kabsch W et al. (1997) The Ras–RasGAP complex: structural basis for GTPase activation and its loss in oncogenic mutants. Science 277: 333–338.

Tesmer JJG, Berman DM, Gilman AG and Sprang SR (1997a) Structure of RGS4 bound to AlF4 activated Giα1: stabilisation of the transition state for GTP hydrolysis. Cell 89: 251–261.

Tesmer JJG, Sunahara RK, Gilman AG and Sprang SR (1997b) Crystal structure of the catalytic domains of adenylyl cyclase in a complex with GsαGTPγS. Science 278: 1907–1916.

Wall MA, Coleman DE, Gilman AG and Sprang SR (1995) The structure of the G protein heterotrimer Giα1β1γ2. Cell 80: 1047–1058.

Wang Y, Jiang Y, Meyering‐Voss M, Sprinzl M and Sigler PB (1997) Crystal structure of the EF‐Tu–EF‐Ts complex from Thermus thermophilus. Nature Structural Biology 4: 650–656.

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.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
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]