GEFs, GAPs, GDIs and effectors: Taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins

Current Opinion in Structural Biology

Volumn 7, Issue 6, 1997, Pages 786-792

  Geyer, Matthias ^a   Wittinghofer, Alfred ^b  

^a MAX PLANCK INSTITUTE FOR MEDICAL RESEARCH   (Germany)

^b MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

GUANINE NUCLEOTIDE BINDING PROTEIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; MAGNESIUM ION; RAS PROTEIN;

ENZYME REGULATION; MOLECULAR CLONING; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN PROTEIN INTERACTION; REVIEW;

EID: 0031452275     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(97)80147-9     Document Type: Article

References (54)

1. Bourne HR, Sanders DA, McCornick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature. 348:1990;125-132.
2. Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature. 349:1991;117-127.
3. Boguski MS, McCormick F. Proteins regulating Ras ans its relatives. Nature. 366:1993;643-654.
4. Gideon P, John J, Frech M, Lautwein A, Clark R, Scheffler JE, Wittinghofer A. Mutational and kinetic analysis of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity. Mol Cell Biol. 12:1992;2050-2056.
5. Diracsvejstrup AB, Sumizawa T, Pfeffer SR. Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI. EMBO J. 16:1997;465-472.
6. Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A. Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 Å resolution: implication for the mechanism of GTP hydrolysis. EMBO J. 9:1990;2351-2359.
7. Milburn MV, Tong L, deVos AM, Brünger A, Yamaizumi Z, Nishimura S, Kim S-H. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science. 247:1990;939-945.
8. Kraulis PJ, Domaille PJ, Campbell-Burk SL, Van Aken T, Laue ED. Solution structure and dynamics of Ras p21-GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy. Biochemistry. 33:1994;3515-3531.
9. Amor JC, Harrison DH, Kahn RA, Ringe D. Structure of the human ADP-ribosylation factor 1 complexed with GDP. Nature. 372:1994;704-708.
10. Greasley SE, Jhoti H, Teahan C, Solari R, Fensome A, Thomas GMH, Cockcroft S, Bax B. The structure of rat ADP-ribosylation factor-1 (ARF-1) complexed to GDP determined from two different crystal forms. Nat Struct Biol. 2:1995;797-806.
11. Scheffzek K, Klebe C, Fritz-Wolf K, Kabsch W, Wittinghofer A. Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form. Nature. 374:1995;378-381.
12. Hirshberg M, Stockley RW, Dodson G, Webb MR. The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue. of special interest Nat Struct Biol. 4:1997;147-152 The first structure of a Rho-like Ras-related GTP-binding protein, which has a 13-residue insert as an additional α helix between strand β5 and helix α4.
13. Feltham JL, Dötsch V, Raza S, Manor D, Cerione RA, Sutcliffe MJ, Wagner G, Oswald RE. Definition of the switch surface in the solution structure of Cdc42Hs. Biochemistry. 36:1997;8755-8766.
14. Wei Y, Zhang Y, Derewenda U, Liu X, Minor W, Nakamoto RK, Somlyo AV, Somlyo AP, Derewenda ZS. Crystal structure of Rho-AGDP: implications for function of GEFs and Clostridium toxins. Nat Struct Biol. 4:1997;699-703.
15. Brachvogel V, Neu M, Metcalf P. Rab7: crystallization of intact and C-terminal truncated constructs complexed with GDP and GppNHp. Proteins. 27:1997;210-212.
16. Geyer M, Schweins T, Herrmann C, Prisner T, Wittinghofer A, Kalbitzer HR. Conformational transitions in p21 ras and in its complexes with the effector protein Raf-RBD and the GTPase activating protein GAP. Biochemistry. 35:1996;10308-10320.
17. H.U J-S, Redfield AG. Conformational and dynamic differences between N-ras P21 bound to GTPγS and to GMPPNP as studied by NMR. Biochemistry. 36:1997;5045-5052.
18. Ito Y, Yamasaki K, Iwahara J, Terada T, Kamiya A, Shirouzu M, Muto Y, Kawai G, Yokoyama S, Laue ED, et al. Regional polysterism in the GTP-bound form of the human c-Ha-Ras protein. Biochemistry. 36:1997;9109-9119.
19. 17O labeling of threonine. Biochemistry. 35:1996;12194-12200.
20. Cherfils J, Ménétrey J, Le Bras G, Janoueix-Lerosey I, de Gunzburg J, Garel J-R, Auzat I. Crystal structures of the small G proteins Rap2A in complex with its substrate GTP, with GDP and with GTPγS. EMBO. 16:1997;5582-5591.
21. Schlichting I, Almo SC, Rapp G, Wilson K, Petratos K, Lentfer A, Wittinghofer A, Kabsch W, Pai EF, Petsko GA, Goody RS. Time resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis. Nature. 345:1990;309-315.
22. Polekhina G, Thirup S, Kjeldgaard M, Nissen P, Lippmann C, Nyborg J. Helix unwinding in the effector region of elongation factor EF-TuGDP. Structure. 4:1995;1141-1151.
23. Nouffer C, Wu S-K, Dascher C, Balch WE. Mss4 does not function as an exchange factor for Rab in endoplasmic reticulum to golgi transport. Mol Biol Cell. 8:1997;1305-1316.
24. Klebe C, Prinz H, Wittinghofer A, Goody RS. The kinetic mechanism of ran-nucleotide exchange catalyzed by RCC1. Biochemistry. 34:1995;12543-12552.
25. Yu H, Schreiber SL. Structure of guanine-nucleotide-exchange factor human Mss4 and identification of its Rab-interacting surface. of special interest Nature. 376:1995;788-791 The solution structure of Mss4 describes a molecule that may not be an efficient GEF but that it binds tightly to the nucleotide-free from of Rab.
26. Herrmann C, Horn G, Spaargaren M, Wittinghofer A. Differential interaction of the Ras family GTP-binding proteins H-Ras, Rap1A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. J Biol Chem. 271:1996;6794-6800.
27. Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC. Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface. Biochemistry. 34:1995;6911-6918.
28. Nassar N, Horn G, Herrmann C, Scherer A, McCormick F, Wittinghofer A. The 2.2Å crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue. Nature. 375:1995;554-560.
29. Block C, Janknecht R, Herrmann C, Nassar N, Wittinghofer A. Quantitative structure/activity analysis correlating Ras/Raf interaction in vitro to Raf activation in vivo. Nat Struct Biol. 3:1996;244-251.
30. Nassar N, Horn G, Herrmann C, Block C, Janknecht R, Wittinghofer A. Ras/Rap effector specificity determined by charge reversal. Nat Struct Biol. 3:1996;723-729.
31. Ghosh S, Xie WQ, Quest AF, Mabrouk GM, Strum JC, Bell RM. The cysteine-rich region of raf-1 kinase contains zinc, translocates to liposomes, and is adjacent to a segment that binds GTP-ras. J Biol Chem. 269:1994;10000-10007.
32. Mott HR, Carpenter JW, Zhong S, Ghosh S, Bell RM, Campbell SL. The solution structure of the Raf-1 cysteine-rich domain: a novel Ras and phospholipid binding site. of special interest Proc Natl Acad Sci USA. 93:1996;8312-8317 The NMR structure of the cysteine-rich domain of c-Raf-1, which is considered to be involved in Ras binding and kinase activation.
33. Geyer M, Herrmann C, Wohlgemuth S, Wittinghofer A, Kalbitzer HR. Structure of the Ras-binding domain of Ral guanine-nucleotide exchange factor: implications for Ras binding and signalling. of special interest Nat Struct Biol. 4:1997;694-699 The structure of the Ras-binding domain of the Ras effector RalGEF is solved using NMR spectroscopy and is found to be homologous to the RBD of c-Raf-1, another Ras effector.
34. Huang L, Weng X, Hofer F, Martin GS, Kim SH. Three dimensional structure of the Ras-interacting domain of RalGDS, a guanine nucleotide stimulator of the Ral protein. of special interest Nat Struct Biol. 4:1997;609-615 The X-ray crystallography structure of the Ras-binding domain of the Ras effector RalGEF, which is homologous to the RBD of c-Raf-1, another Ras effector. (See [33]).
35. rap1. Cell. 65:1991;1033-1042.
36. Ahmadian MR, Wiesmüller L, Lautwein A, Bischoff FR, Wittinghofer A. Structural differences in the minimal catalytic domains of the GTPase-activating Protein p21(GAP) and neurofibromin. J Biol Chem. 271:1996;16409-16415.
37. Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A. Crystal structure of the GTPase-activating domain of human p120GAP and implication for the interaction with Ras. of special interest Nature. 384:1996;591-596 This paper shows the structure of RasGAP with the conserved residues centered around a shallow groove and shows how Ras may bind to it.
38. Musacchio A, Cantley LC, Harrison SC. Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85α subunit. of special interest Proc Natl Acad Sci USA. 93:1996;14373-14378 This paper shows the structure of the RhoGAP domain of a subunit of Pl(3) kinase, which is inactive as a RhoGAP.
39. Barrett T, Xiao B, Dodson EJ, Dodson G, Ludbrook SB, Nurmahomed K, Gamblin SJ, Musacchio A, Smerdon SJ, Eccleston JF. The structure of the GTPase-activating domain from p50rhoGAP. of special interest Nature. 385:1997;458-461 The author show the helical nature of RhoGAP and suggest a binding site for Rho and residues of GAP involved in the activation.
40. Maegley KA, Admiraal SJ, Herschlag D. Ras-catalyzed hydrolysis of GTP: a new perspective from model studies. Proc Natl Acad Sci USA. 93:1996;8160-8166.
41. Schweins T, Geyer M, Kalbitzer HR, Wittinghofer A, Warshel A. Linear free energy relationships in the intrinsic and GTPase activating protein-stimulated guanosine 5′-triphosphate hydrolysis of p21ras. Biochemistry. 35:1996;14225-14231.
42. 4-. Nature. 372:1994;276-279.
43. iα1 and the mechanism of GTP hydrolysis. Science. 265:1994;1405-1412.
44. Mittal R, Ahmadian MR, Goody RS, Wittinghofer A. Formation af a transition-state analog of the Ras GTPase reaction by RasGDP, tetrafluoroaluminate, and GTPase-activating proteins. Science. 273:1996;115-117.
45. Scheffzek K, Ahmadian MR, Kabsch W, Wiesmüller L, Lautwein A, Schmitz F, Wittinghofer A. The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. of outstanding interest Science. 277:1997;333-338 The structure of the complex between Ras and RasGAP in the transition state shows how RasGAP catalyzes GTP hydrolysis on Ras, and why oncogenic Ras is insensitive to its activation.
46. Rittinger K, Walker PA, Eccleston JF, Nurmahomed K, Laue E, Owen D, Gamblin SJ, Smerdon SJ. Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP. of outstanding interest Nature. 388:1997;693-697 The crystal structure of the complex between RhoGAP and Cdc42 in the ground GppNHp-bound state shows that interact mainly via the switch regions of Cdc42.
47. -, such that the resulting structure is similar to the Ras·Ras·GAP complex.
48. Schalk I, Zeng K, Wu SK, Stura EA, Matteson J, Huang M, Tandon A, Wilson IA, Balch WE. Structure and mutational analysis of Rab GDP-dissociation inhibitor. of outstanding interest Nature. 381:1996;42-48 The paper shows RabGDI to be a two-domain structure with three conserved sequence regions clustered at the tip of the molecule and explores the interaction with Rab using structure-based mutational analysis.
49. Isomura M, Kikuchi A, Ohga N, Takai Y. Regulation of binding of rhoB p20 to membranes by its specific regulatory protein, GDP dissociation inhibitor. Oncogene. 6:1991;119-124.
50. Keep NH, Barnes M, Barsukov I, Badii R, Lian LY, Segal AW, Moody PCE, Roberts GCK. A modulator of rho family G proteins, rhoGDI, binds these G proteins via an immunoglobulin-like domain and a flexible N-terminal arm. of outstanding interest Structure. 5:1997;623-633 A combination of crystal and NMR structure determinations show the mode of binding of RhoGDI to Rac (see [51]).
51. Gosser YQ, Nomanbhoy TK, Aghazadeh B, Manor D, Combs C, Cerione RA, Rosen MK. C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminals inhibitory peptide to GTPases. of outstanding interest Nature. 387:1997;814-819 The NMR structure of RhoGDI, supported by fluorescence studies, shows how the protein binds to Cdc42 and inhibits its GDP dissociation via two different regions of the molecule and also shows the lipid-binding pocket (see also [50]).
52. Park H-W, Boduluri SR, Moomaw JF, Casey PJ, Beese LS. Crystal structure of protein farnesyltransferase at 2.25 Å resolution. of outstanding interest Science. 275:1997;1800-1804 The only structure of a prenyltransferase known to date. It shows how this pharmacologically very important protein might bind substrates.
53. Moore MS, Blobel G. Purification of a Ran-interacting protein that is required for protein import into the nucleus. Proc Natl Acad Sci USA. 91:1994;10212-10216.
54. Bullock TL, Clarkson WD, Kent HM, Stewart M. The 1.6 Å resolution crystal structure of nuclear transport factor 2 (NTF2). of special interest J Mol Biol. 260:1996;422-431 The structure of an effector that specifically recognizes the GDP-bound form of Ran.