Structural basis for recruitment of RILP by small GTPase Rab7

被引:114
作者
Wu, MS
Wang, TL
Loh, E
Hong, WJ
Song, HW
机构
[1] Natl Univ Singapore, Inst Mol & Cell Biol, Lab Membrane Biol, Singapore 138673, Singapore
[2] Natl Univ Singapore, Inst Mol & Cell Biol, Lab Macromol Struct, Singapore 117548, Singapore
[3] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore
关键词
membrane trafficking; Rab proteins; Rab7; Rab-effector complex; RILP;
D O I
10.1038/sj.emboj.7600643
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
Rab7 regulates vesicle traffic from early to late endosomes, and from late endosomes to lysosomes. The crystal structure of Rab7-GTP in complex with the Rab7 binding domain of RILP reveals that Rab7 interacts with RILP specifically via two distinct areas, with the first one involving the switch and interswitch regions and the second one consisting of RabSF1 and RabSF4. Disruption of these interactions by mutations abrogates late endosomal/lysosomal targeting of Rab7 and RILP. The Rab7 binding domain of RILP forms a coiled-coil homodimer with two symmetric surfaces to interact with two separate Rab7GTP molecules, forming a dyad configuration of Rab7 RILP2-Rab7. Mutations that disrupt RILP dimerization also abolish its interactions with Rab7-GTP and late endosomal/lysosomal targeting, suggesting that the dimeric form of RILP is a functional unit. Structural comparison suggests that the combined use of RabSF1 and RabSF4 with the switch regions may be a general mode of action for most Rab proteins in regulating membrane trafficking.
引用
收藏
页码:1491 / 1501
页数:11
相关论文
共 42 条
[1]   Multiple regions contribute to membrane targeting of Rab GTPases [J].
Ali, BR ;
Wasmeier, C ;
Lamoreux, L ;
Strom, M ;
Seabra, MC .
JOURNAL OF CELL SCIENCE, 2004, 117 (26) :6401-6412
[2]   Molecular basis for Rab prenylation [J].
Alory, C ;
Balch, WE .
JOURNAL OF CELL BIOLOGY, 2000, 150 (01) :89-103
[3]   CDNA CLONING OF COMPONENT-A OF RAB GERANYLGERANYL TRANSFERASE AND DEMONSTRATION OF ITS ROLE AS A RAB ESCORT PROTEIN [J].
ANDRES, DA ;
SEABRA, MC ;
BROWN, MS ;
ARMSTRONG, SA ;
SMELAND, TE ;
CREMERS, FPM ;
GOLDSTEIN, JL .
CELL, 1993, 73 (06) :1091-1099
[4]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[5]   INTERACTIONS OF 3 DOMAINS DISTINGUISHING THE RAS-RELATED GTP-BINDING PROTEINS YPT1 AND SEC4 [J].
BRENNWALD, P ;
NOVICK, P .
NATURE, 1993, 362 (6420) :560-563
[6]  
Brunger AT, 1998, ACTA CRYSTALLOGR D, V54, P905, DOI 10.1107/s0907444998003254
[7]   Rab7: A key to lysosome biogenesis [J].
Bucci, C ;
Thomsen, P ;
Nicoziani, P ;
McCarthy, J ;
van Deurs, B .
MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (02) :467-480
[8]   Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes [J].
Cantalupo, G ;
Alifano, P ;
Roberti, V ;
Bruni, CB ;
Bucci, C .
EMBO JOURNAL, 2001, 20 (04) :683-693
[9]   HYPERVARIABLE C-TERMINAL DOMAIN OF RAB PROTEINS ACTS AS A TARGETING SIGNAL [J].
CHAVRIER, P ;
GORVEL, JP ;
STELZER, E ;
SIMONS, K ;
GRUENBERG, J ;
ZERIAL, M .
NATURE, 1991, 353 (6346) :769-772
[10]   Rab7 prevents growth factor-independent survival by inhibiting cell-autonomous nutrient transporter expression [J].
Edinger, AL ;
Cinalli, RM ;
Thompson, CB .
DEVELOPMENTAL CELL, 2003, 5 (04) :571-582