Geranylgeranylation of Rab GTPases

被引:175
作者
Leung, KF [1 ]
Baron, R [1 ]
Seabra, MC [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, London SW7 2AZ, England
关键词
prenyl transferases; Rab escort protein; GDP dissociation inhibitor; geranylgeranyl;
D O I
10.1194/jlr.R500017-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 REP binds Rab and presents it to RGGT. After geranylgeranylation of Rab C-terminal cysteines, 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 has helped to refine this model and provided further insights. The hydrophobic prenyl binding pocket of RGGT and geranylgeranyl transferase type-I (GGT-I) differs from that of farnesyl transferase ( FT). A bulky tryptophan residue in FT restricts the size of the pocket, whereas in RGGT and GGT-I, this position is occupied by smaller residues. A highly conserved phenylalanine in REP, which is absent in RabGDI, is critical for the formation of the REP: RGGT complex. Finally, a geranylgeranyl binding site conserved in REP and RabGDI has been identified within helical domain II. The postprenylation 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 subject of future studies.
引用
收藏
页码:467 / 475
页数:9
相关论文
共 60 条
[41]   DEFICIENT GERANYLGERANYLATION OF RAM/RAB27 IN CHOROIDEREMIA [J].
SEABRA, MC ;
HO, YK ;
ANANT, JS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (41) :24420-24427
[42]   New insights into the pathogenesis of choroideremia: A tale of two REPs [J].
Seabra, MC .
OPHTHALMIC GENETICS, 1996, 17 (02) :43-46
[43]   Nucleotide dependence of Rab geranylgeranylation - Rab escort protein interacts preferentially with GDP-bound Rab [J].
Seabra, MC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (24) :14398-14404
[44]  
SEABRA MC, 1992, J BIOL CHEM, V267, P14497
[45]  
SEGEV N, 2001, SCI STKE, pRE11, DOI DOI 10.1126/STKE.2001.100.RE11
[46]  
Shen F, 1996, J BIOL CHEM, V271, P3692
[47]   GERANYLGERANYLATED RAB PROTEINS TERMINATING IN CYS-ALA-CYS, BUT NOT CYS-CYS, ARE CARBOXYL-METHYLATED BY BOVINE BRAIN MEMBRANES IN-VITRO [J].
SMELAND, TE ;
SEABRA, MC ;
GOLDSTEIN, JL ;
BROWN, MS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (22) :10712-10716
[48]   Structure of mammalian protein geranylgeranyltransferase type-I [J].
Taylor, JS ;
Reid, TS ;
Terry, KL ;
Casey, PJ ;
Beese, LS .
EMBO JOURNAL, 2003, 22 (22) :5963-5974
[49]   Phosphoisoprenoid binding specificity of geranylgeranyltransferase type II [J].
Thomä, NH ;
Iakovenko, A ;
Owen, D ;
Scheidig, AS ;
Waldmann, H ;
Goody, RS ;
Alexandrov, K .
BIOCHEMISTRY, 2000, 39 (39) :12043-12052
[50]   Double prenylation by RabGGTase can proceed without dissociation of the mono-prenylated intermediate [J].
Thomä, NH ;
Niculae, A ;
Goody, RS ;
Alexandrov, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (52) :48631-48636