Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product

Cell. 1992 Sep 18;70(6):1049-57. doi: 10.1016/0092-8674(92)90253-9.


Rab geranylgeranyl transferase (GG transferase) from rat brain contains two components, A and B. Component B comprises polypeptides of 60 and 38 kd. Here we report the purification of component A, a single 95 kd polypeptide. The holoenzyme attaches 3H-geranylgeranyl to cysteines in two GTP-binding proteins, Rab3A and Rab1A. The reaction is abolished when both cysteines in the COOH-terminal CysCys sequence of Rab1A are mutated to serines. The mutant protein inhibits transfer of 3H-geranylgeranyl to wild-type Rab1A and Rab3A, suggesting that the enzyme recognizes conserved sequences distinct from the COOH-terminus. Six peptides from rat component A show striking similarity to the product of the defective gene in choroideremia, an X-linked retinal degeneration disease. The choroideremia protein resembles Rab3A GDI, which binds Rab3A. We hypothesize that component A binds conserved sequences in Rab and that component B transfers geranylgeranyl. A defect in this reaction may cause choroideremia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / enzymology
  • Choroideremia / genetics*
  • Chromatography, Liquid / methods
  • Molecular Sequence Data
  • Mutation
  • Rats
  • Rats, Inbred Strains
  • Sequence Homology, Nucleic Acid
  • Transferases / chemistry
  • Transferases / isolation & purification*


  • Transferases
  • Alkyl and Aryl Transferases
  • Rab geranylgeranyltransferase