Purification of component A of Rab geranylgeranyl transferase

Possible identity with the choroideremia gene product

Miguel C. Seabra, Michael S. Brown, Clive A. Slaughter, Thomas C. Südhof, Joseph L. Goldstein

Research output: Contribution to journalArticle

217 Citations (Scopus)

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 wildtype 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.

Original languageEnglish (US)
Pages (from-to)1049-1057
Number of pages9
JournalCell
Volume70
Issue number6
DOIs
StatePublished - Sep 18 1992
Externally publishedYes

Fingerprint

Choroideremia
rab3A GTP-Binding Protein
Purification
Conserved Sequence
Genes
rab1 GTP-Binding Proteins
Peptides
Cysteine
Rats
Guanine Nucleotide Dissociation Inhibitors
Retinal Diseases
Retinal Degeneration
Holoenzymes
Mutant Proteins
Serine
Brain
Defects
Enzymes
Rab geranylgeranyltransferase
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Purification of component A of Rab geranylgeranyl transferase : Possible identity with the choroideremia gene product. / Seabra, Miguel C.; Brown, Michael S.; Slaughter, Clive A.; Südhof, Thomas C.; Goldstein, Joseph L.

In: Cell, Vol. 70, No. 6, 18.09.1992, p. 1049-1057.

Research output: Contribution to journalArticle

Seabra, Miguel C. ; Brown, Michael S. ; Slaughter, Clive A. ; Südhof, Thomas C. ; Goldstein, Joseph L. / Purification of component A of Rab geranylgeranyl transferase : Possible identity with the choroideremia gene product. In: Cell. 1992 ; Vol. 70, No. 6. pp. 1049-1057.
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N2 - 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 wildtype 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.

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