Structural basis for recruitment of RILP by small GTPase Rab7

EMBO J. 2005 Apr 20;24(8):1491-501. doi: 10.1038/sj.emboj.7600643. Epub 2005 Mar 31.

Abstract

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 Rab7-GTP molecules, forming a dyad configuration of Rab7-RILP(2)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • Dimerization
  • Endosomes / metabolism
  • Humans
  • Lysosomes / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein Structure, Quaternary*
  • Sequence Alignment
  • Transport Vesicles / metabolism*
  • Two-Hybrid System Techniques
  • rab GTP-Binding Proteins / chemistry*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • RILP protein, human
  • Rilp protein, mouse
  • rab7 protein
  • rab GTP-Binding Proteins

Associated data

  • PDB/1YHN