title: Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
authors.forename: M C
authors.initials: MC
authors.lastname: Seabra
authors.forename: M S
authors.initials: MS
authors.lastname: Brown
authors.forename: C A
authors.initials: CA
authors.lastname: Slaughter
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: J L
authors.initials: JL
authors.lastname: Goldstein
mesh_terms: D019883:Alkyl and Aryl Transferases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D015794:Choroideremia / Q000235:genetics*; D002853:Chromatography, Liquid / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D012689:Sequence Homology, Nucleic Acid; D014166:Transferases / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D014166:Transferases; D019883:Alkyl and Aryl Transferases; C075607:Rab geranylgeranyltransferase