Phosphate-binding loop and Rab-GTPase function: Mutations at Ser29 and Ala30 of Rab5 lead to loss-of-function as well as gain-of-function phenotype

Biochemical Journal

Volumn 355, Issue 3, 2001, Pages 681-689

  Li, Guangpu ^a   Liang, Zhimin ^a  

^a UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

Author keywords

Endocytosis; GTP binding; GTP hydrolysis; Ras; Structure function relationship

Indexed keywords

AMINO ACIDS; BIOLOGICAL MEMBRANES; BIOLOGICAL ORGANS; CELL CULTURE; ENZYMES; MUTAGENESIS;

PHOSPHATE-BINDING LOOP;

BIOCHEMISTRY;

ALANINE; GLYCINE; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE TRIPHOSPHATASE; HORSERADISH PEROXIDASE; MUTANT PROTEIN; NUCLEOTIDE; PHOSPHATE BINDING AGENT; RAB PROTEIN; SERINE;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; ENDOCYTOSIS; ENDOSOME; ENZYME ACTIVITY; HAMSTER; KIDNEY CELL; MUTATION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; STRUCTURE ACTIVITY RELATION;

ANIMALIA; ARMORACIA RUSTICANA; CRICETINAE;

EID: 0035339644     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/bj3550681     Document Type: Article

References (37)

1. 1 Bourne, H. R., Sanders, D. A. and McCormick, F. (1990) The GTPase superfamily: a conserved switch for diverse cell functions. Nature (London) 348, 125-132
2. 2 Moss, J. and Vaughan, M. (1998) Molecules in the ARF orbit. J. Biol. Chem. 273, 21431-21434
3. 3 Novick, P. and Zerial, M. (1997) The diversity of Rab proteins in vesicle transport. Curr. Opin. Cell Biol. 9, 496-504
4. 4 Nuoffer, C. and Balch, W. E. (1994) GTPases: multifunctional molecular switches regulating vesicular traffic. Annu. Rev. Biochem. 63, 949-990
5. 5 Barbacid, M. (1987) ras genes. Annu. Rev. Biochem. 56, 779-827
6. 6 Krengel, U., Schlichting, L., Scherer, A., Schumann, R., French, M., John, J., Kabsch, W., Pai, E. F. and Wittinghofer, A. (1990) Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell 62, 539-548
7. 7 Prive, G. G., Milburn, M. V., Tong, L., deVos, A. M., Yamaizumi, Z., Nishimura, S. and Kim, S.-H. (1992) X-ray crystal structures of transforming p21 ras mutants suggest a transition-state stabilization mechanism for GTP hydrolysis. Proc. Natl. Acad. Sci. U.S.A. 89, 3649-3653
8. 8 Scheffzek, K., Ahmadian, M. R., Kabsch, W., Wiesmullet, L., Lautwein, A., Schmitz, F. and Wittinghofer, A. (1997) The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 277, 333-338
9. 9 Seeburg, P. H., Colby, W. W., Capon, D. J., Goedel, D. V. and Levinson, A. D. (1984) Biological properties of human c-Ha-ras 1 genes mutated at codon 12. Nature (London) 312, 71-75
10. 10 Chung, H. H., Benson, D. R. and Schultz, P. G. (1993) Probing the structure and mechanism of Ras protein with an expanded genetic code. Science 259, 806-809
11. 11 Lowy, D. R. and Willumsen, B. M, (1993) Function and regulation of Ras. Annu. Rev. Biochem. 62, 851-891
12. 12 Bos, J. L. (1989) ras oncogenes in human cancer: a review. Cancer Res. 49, 4682-4689
13. 13 Barbieri, M. A., Li, G., Colombo, M. I. and Stahl, P. D. (1994) Rab5, an early acting endosomal GTPase, supports in vitro endosome fusion without GTP hydrolysis. J. Biol. Chem. 269, 18720-18722
14. 14 Bucci, C., Parton, R. G., Mather, I. M., Stunnenberg, H., Simons, K., Hoflack, B. and Zerial, M. (1992) The small GTPase Rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70, 715-728
15. 15 Gorvel, J.-P., Chavrier, P., Zerial, M. and Gruenberg, J. (1991) rab5 controls early endosome fusion in vitro. Cell 64, 915-925
16. 16 Hoffenberg, S., Sanford, J. C., Liu, S., Daniel, D. S., Tuvin, M., Knoll, B. J., Wessling-Resnick, M. and Dickey, B. F. (1995) Biochemical and functional characterization of a recombinant GTPase, Rab5, and two of its mutants. J. Biol. Chem. 270, 5048-5056
17. 17 Li, G. and Stahl, P. D. (1993) Structure-function relationship of the small GTPase Rab5. J. Biol. Chem. 268, 24475-24480
18. 18 Stenmark, H., Parton, R. G., Steele-Mortimer, O., Lutcke, A., Gruenberg, J. and Zerial, M. (1994) Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J. 13, 1287-1296
19. 19 Zahraoul, A., Touchot, N., Chardin, P. and Tavitian, A. (1989) The human rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion. J. Biol. Chem. 264, 12394-12401
20. 20 Liu, K. and Li, G. (1998) Catalytic domain of the p120 Ras GAP binds to Rab5 and stimulates its GTPase activity. J. Biol. Chem. 273, 10087-10090
21. 21 Chen, B. and Przybyla, A. E. (1994) An efficient site-directed mutagenesis method based on PCR. BioTechniques 17, 657-659
22. 30 of Rab5. Biochem. J. 346, 501-508
23. 23 Frolov, I., Hoffman, T. A., Pragai, B. M., Dryga, S. A., Huang, H. V., Schlesinger, S. and Rice, C. M. (1996) Alphavirus-based expression vectors: strategies and applications, Proc. Natl. Acad. Sci. U.S.A. 93, 11371-11377
24. 24 Li, G., Barbieri, M. A., Colombo, M. I. and Stahl, P. D. (1994) Structural features of the GTP-bindlng defective Rab5 mutants required for their inhibitory activity on endocytosis. J. Biol. Chem. 269, 14631-14635
25. 25 McLauchlan, H., Newell, J., Morrice, N., Osborne, A., West, M. and Smythe, E. (1998) A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits. Curr. Biol. 8, 34-45
26. 26 Imamura, H., Takaishi, K., Nakano, K., Kodama, A., Oishi, H., Shiozaki, H., Monden, M., Sasaki, T. and Takai, Y. (1998) Rho and Rab small G proteins coordinately reorganize stress fibers and local adhesions in MDCK cells. Mol. Biol. Cell 9, 2561-2575
27. 27 Spaargaren, M. and Bos, J. L. (1999) Rab5 induces Rac-independent lamellipodia formation and cell migration. Mol. Biol. Cell 10, 3239-3250
28. 28 Kabcenell, A. K., Goud, B., Northup, J. and Novick, P. J. (1990) Binding and hydrolysis of guanine nucleotides by Sec4p, a yeast protein involved in the regulation of vesicular traffic. J. Biol. Chem. 265, 9366-9372
29. 2+ on the structure and function of Rab5. J. Biol Chem. 271, 1322-1328
30. 30 Horluchi, H., Lippe, R., McBride, H. M., Rubino, M., Woodman, P., Stenmark, H., Rybin, V., Wilm, M., Ashman, K., Mann, M. and Zerial, M. (1997) A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function. Cell 90, 1149-1159
31. 31 Xiad, G. H., Shoarinejad, F., Jin, F., Golemis, E. A. and Yeung, R. S. (1997) The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J. Biol. Chem. 272, 6097-6100
32. 32 McBride, H. M., Rybin, V., Murphy, C., Giner, A., Teasdale, R. and Zerial, M. (1999) Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13. Cell 98, 377-386
33. 33 Seabra, M. C., Goldstein, J. L., Südhof, T. C. and Brown, M. S. (1992) Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys, J. Biol. Chem. 267, 14497-14503
34. 34 Burstein, E. S., Brondyk, W. H. and Macara, I. G. (1992) Amino acid residues in the ras-like GTPase rab3A that specify sensitivity to factors that regulate the GTP/GDP cycling of rab3A. J. Biol. Chem. 267, 22715-22718
35. 35 Dumas, J. J., Zhu, Z., Connolly, J. L. and Lambright, D. G. (1999) Structural basis of activation and GTP hydrolysis in Rab proteins. Structure 7, 413-423
36. 36 Pai, E. F., Krengel, U., Petsko, G. A., Goody, R. S., Kabsch, W. and Wittinghofer, A. (1990) Refined crystal structure of the triphosphate conformation of H-ras p21 at 1,35 A resolution: implications for the mechanism of GTP hydrolysis. EMBO J. 9, 2351-2359
37. 2+? BioEssays 20, 516-521