Structure of Rab escort protein-1 in complex with Rab geranylgeranyltransferase

Mol Cell. 2003 Feb;11(2):483-94. doi: 10.1016/s1097-2765(03)00044-3.


Posttranslational geranylgeranylation of Rab GTPases is catalyzed by Rab geranylgeranyltransferase (RabGGTase), which consists of a catalytic alpha/beta heterodimer and an accessory Rab escort protein (REP). The crystal structure of isoprenoid-bound RabGGTase complexed to REP-1 has been solved to 2.7 A resolution. The complex interface buries a surprisingly small surface area of ca. 680 A and is unexpectedly formed by helices 8, 10, and 12 of the RabGGTase alpha subunit and helices D and E of REP-1. We demonstrate that the affinity of RabGGTase for REP-1 is allosterically regulated by phosphoisoprenoid via a long-range trans-domain signal transduction event. Comparing the structure of REP-1 with the closely related RabGDI, we conclude that the specificity of the REP:RabGGTase interaction is defined by differently positioned phenylalanine residues conserved in the REP and GDI subfamilies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / chemistry*
  • Alkyl and Aryl Transferases / genetics
  • Alkyl and Aryl Transferases / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Guanine Nucleotide Dissociation Inhibitors / chemistry
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism
  • In Vitro Techniques
  • Lipid Metabolism
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • rab GTP-Binding Proteins / chemistry*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism
  • rab3A GTP-Binding Protein / chemistry
  • rab3A GTP-Binding Protein / genetics
  • rab3A GTP-Binding Protein / metabolism


  • GDP dissociation inhibitor 1
  • Guanine Nucleotide Dissociation Inhibitors
  • Macromolecular Substances
  • Alkyl and Aryl Transferases
  • Rab geranylgeranyltransferase
  • rab GTP-Binding Proteins
  • rab3A GTP-Binding Protein