G Proteins

Jeroen R Mesters, Institute of Molecular Biotechnology, Jena, Germany
Tanis Hogg, Institute of Molecular Biotechnology, Jena, Germany
Rolf Hilgenfeld, Institute of Molecular Biotechnology, Jena, Germany

Published online: April 2001

DOI: 10.1038/npg.els.0000657

The G proteins, or GTP-binding proteins, can be classified into three major groups: the large mammalian G 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 Gi–GDP–G (a) and active Gs–GTP in complex with adenylyl cyclase (b). Colours are as follows: G (a) and adenylyl cyclase (b) are shown in green, G is in yellow and G 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 Gi complex with GDP– Mg2+ and AlF4–.
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 References
    Abel K, Yoder MD, Hilgenfeld R and Jurnak F (1996) An to 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.
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    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 Gi1: 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 GsGTPS. Science 278: 1907–1916.
    Wall MA, Coleman DE, Gilman AG and Sprang SR (1995) The structure of the G protein heterotrimer Gi112. 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.
    book 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.

Related Sub-Topics:

Intracellular and Extracellular Signalling | Basic Cell Biology, Protein, RNA and DNA | Signal Transduction | Protein Structure | Translation and Protein synthesis | Cell Signalling | Proteins: Structure, Function, Metabolism
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Article Title: G Proteins
 
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]