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.
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Choroideremia is caused by mutations in the REP1 (aka CHM) gene, which encodes RAB escort protein-1.
“Choroideremia is caused by mutations in the REP1 (aka CHM) gene, which encodes RAB escort protein-1 (Cremers et al., 1990; Seabra et al., 1992).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Seabra et al., 1992
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- Authors
- Seabra, M. C., Brown, M. S., Slaughter, C. A., Südhof, T. C., & Goldstein, J. L.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1992-09
- Volume
- 70
- Issue
- 6
- Pages
- 1049-1057
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2023062131
- Cited by
- 300
- References
- 31
- Citations by year
- 2026: 4 · 2025: 3 · 2023: 1 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 3 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 7
- FWCI
- 11.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Geological Survey
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- Rab geranylgeranyltransferase, choroideremia, Rab3A, Rab1A, geranylgeranylation, G proteins, cysteine mutants, X-linked retinal degeneration, protein purification
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Brain, Chromatography, Liquid, Molecular Sequence Data, Mutation, Rats, Inbred Strains, Sequence Homology, Nucleic Acid, Transferases, Choroideremia, Alkyl and Aryl Transferases, Rats
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