|
 |
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print January 9, 2006
J. Lipid Res., doi:10.1194/jlr.R500017-JLR200
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Biomedical Sciences, Imperial College London, London, London SW7 2AZ
Corresponding Author: m.seabra{at}imperial.ac.uk
Rab GTPases require special machinery for protein prenylation, which include Rab Escort Protein (REP) and Rab Geranylgeranyl Transferase (RGGT). The current model of Rab geranylgeranylation proposes that the Rab protein must bind REP, which presents the Rab to RGGT. Following geranylgeranylation of C-terminal cysteines in Rab, REP delivers the prenylated protein to membranes. The REP-like protein, Rab GDP dissociation inhibitor (RabGDI) then recycles the prenylated Rab between the membrane and the cytosol. The recent solution of crystal structures of the Rab prenylation machinery have helped to refine this model and provide further insights. The hydrophobic prenyl binding site of RGGT is similar to that of geranylgeranyl transferase type-I (GGT-I) but differs from farnesyl transferase (FT). At the bottom of the hydrophobic isoprenyl-binding pocket, a bulky Trp residue in FT prevents binding of the longer geranylgeranyl pyrophosphate group whereas in GGT-I and RGGT this position is occupied by the smaller residues Thr and Ser, respectively. At the REP:RGGT interface, a highly conserved Phe in REP, which is absent in RabGDI, plays a critical role in the formation of the REP:RGGT complex and may explain the inability of RabGDI to complex with RGGT. A geranylgeranyl-binding site in REP and RabGDI has been identified within domain II. However, as most Rabs undergo double geranylgeranylation, it is still unclear how and where the second geranylgeranyl group is stabilised. The post-prenylation events, including the specific targeting of Rabs to target membranes and the requirement for single versus double-geranylgeranylation by different Rabs remain obscure and should be the object of future studies.
Revised on January 5, 2006
Accepted on January 9, 2006
Geranylgeranylation of Rab GTPases
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Morck, L. Olsen, C. Kurth, A. Persson, N. J. Storm, E. Svensson, J.-O. Jansson, M. Hellqvist, A. Enejder, N. J. Faergeman, et al. Statins inhibit protein lipidation and induce the unfolded protein response in the non-sterol producing nematode Caenorhabditis elegans PNAS, October 27, 2009; 106(43): 18285 - 18290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Branham, M. A. Bustos, G. A. De Blas, H. Rehmann, V. E. P. Zarelli, C. L. Trevino, A. Darszon, L. S. Mayorga, and C. N. Tomes Epac Activates the Small G Proteins Rap1 and Rab3A to Achieve Exocytosis J. Biol. Chem., September 11, 2009; 284(37): 24825 - 24839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, Y. Zhou, R. Jin, and C. Chan Reconstruct modular phenotype-specific gene networks by knowledge-driven matrix factorization Bioinformatics, September 1, 2009; 25(17): 2236 - 2243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lu, L. Chan, H. D.G. Fiji, R. Dahl, O. Kwon, and F. Tamanoi In vivo antitumor effect of a novel inhibitor of protein geranylgeranyltransferase-I Mol. Cancer Ther., May 1, 2009; 8(5): 1218 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Baron, R. Tavare, A. C. Figueiredo, K. M. Blazewska, B. A. Kashemirov, C. E. McKenna, F. H. Ebetino, A. Taylor, M. J. Rogers, F. P. Coxon, et al. Phosphonocarboxylates Inhibit the Second Geranylgeranyl Addition by Rab Geranylgeranyl Transferase J. Biol. Chem., March 13, 2009; 284(11): 6861 - 6868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Domoki, B. Kis, T. Gaspar, J. A. Snipes, J. S. Parks, F. Bari, and D. W. Busija Rosuvastatin induces delayed preconditioning against oxygen-glucose deprivation in cultured cortical neurons Am J Physiol Cell Physiol, January 1, 2009; 296(1): C97 - C105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Figueiredo, C. Wasmeier, A. K. Tarafder, J. S. Ramalho, R. A. Baron, and M. C. Seabra Rab3GEP Is the Non-redundant Guanine Nucleotide Exchange Factor for Rab27a in Melanocytes J. Biol. Chem., August 22, 2008; 283(34): 23209 - 23216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Watanabe, H. D. G. Fiji, L. Guo, L. Chan, S. S. Kinderman, D. J. Slamon, O. Kwon, and F. Tamanoi Inhibitors of Protein Geranylgeranyltransferase I and Rab Geranylgeranyltransferase Identified from a Library of Allenoate-derived Compounds J. Biol. Chem., April 11, 2008; 283(15): 9571 - 9579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sakamoto, T. Honda, S. Yokoya, S. Waguri, and J. Kimura Rab-small GTPases are involved in fluvastatin and pravastatin-induced vacuolation in rat skeletal myofibers FASEB J, December 1, 2007; 21(14): 4087 - 4094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Schwartz, C. Cao, O. Pylypenko, A. Rak, and A. Wandinger-Ness Rab GTPases at a glance J. Cell Sci., November 15, 2007; 120(22): 3905 - 3910. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schmandke, A. Schmandke, and S. M. Strittmatter ROCK and Rho: Biochemistry and Neuronal Functions of Rho-Associated Protein Kinases Neuroscientist, October 1, 2007; 13(5): 454 - 469. [Abstract] [PDF]
|
|
|
|
 |
|
 J. A. Valentijn, L. van Weeren, A. Ultee, and A. J. Koster Novel localization of Rab3D in rat intestinal goblet cells and Brunner's gland acinar cells suggests a role in early Golgi trafficking Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G165 - G177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. Leung, R. Baron, B. R. Ali, A. I. Magee, and M. C. Seabra Rab GTPases Containing a CAAX Motif Are Processed Post-geranylgeranylation by Proteolysis and Methylation J. Biol. Chem., January 12, 2007; 282(2): 1487 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Roelofs, K. Thompson, S. Gordon, and M. J. Rogers Molecular mechanisms of action of bisphosphonates: current status. Clin. Cancer Res., October 15, 2006; 12(20): 6222s - 6230s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. J. Holt, F. Gallo, and G. M. Griffiths Regulating secretory lysosomes. J. Biochem., July 1, 2006; 140(1): 7 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Lane and L. S. Beese Thematic review series: Lipid Posttranslational Modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I J. Lipid Res., April 1, 2006; 47(4): 681 - 699. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |