Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease

Cell. 2004 Jun 11;117(6):749-60. doi: 10.1016/j.cell.2004.05.017.


Members of the RabGDI/REP family serve as multifunctional regulators of the Rab family of GTP binding proteins. Mutations in members of this family, such as REP-1, lead to abnormalities, including progressive retinal degradation (choroideremia) in humans. The crystal structures of the REP-1 protein in complex with monoprenylated or C-terminally truncated Rab7 proteins revealed that Rab7 interacts with the Rab binding platform of REP-1 via an extended interface involving the Switch 1 and 2 regions. The C terminus of the REP-1 molecule functions as a mobile lid covering a conserved hydrophobic patch on the surface of REP-1 that in the complex coordinates the C terminus of Rab proteins. Using semisynthetic fluorescent Rab27A, we demonstrate that although Rab27A can be prenylated by REP-2, this reaction can be effectively inhibited by other Rab proteins, providing a possible explanation for the accumulation of unprenylated Rab27A in choroideremia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alkyl and Aryl Transferases / chemistry
  • Alkyl and Aryl Transferases / genetics
  • Alkyl and Aryl Transferases / metabolism*
  • Binding Sites / physiology
  • Carrier Proteins / metabolism
  • Catalytic Domain / physiology
  • Choroideremia / genetics
  • Choroideremia / metabolism*
  • Humans
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Structure
  • Protein Binding / physiology
  • Protein Prenylation / physiology*
  • Protein Structure, Tertiary / physiology
  • Terpenes / metabolism*
  • rab GTP-Binding Proteins / chemistry
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab27 GTP-Binding Proteins


  • Adaptor Proteins, Signal Transducing
  • CHM protein, human
  • CHML protein, human
  • Carrier Proteins
  • Macromolecular Substances
  • Terpenes
  • rab27 GTP-Binding Proteins
  • rab7 protein
  • Alkyl and Aryl Transferases
  • RAB27A protein, human
  • rab GTP-Binding Proteins

Associated data

  • PDB/1VG9
  • PDB/IVG0
  • PDB/IVG1
  • PDB/IVG8