TY - JOUR
T1 - Purification of component A of Rab geranylgeranyl transferase
T2 - Possible identity with the choroideremia gene product
AU - Seabra, Miguel C.
AU - Brown, Michael S.
AU - Slaughter, Clive A.
AU - Südhof, Thomas C.
AU - Goldstein, Joseph L.
N1 - Funding Information:
We thank Veronica Martinez, Richard Gibson, and Debra Noble-Morgan for their excellent technical assistance. Carolyn Moomaw and Joan Hsu provided invaluable help with the amino acid sequence analysis. This research was supported by research grants from the National Institutes of Health (HL 20948), the Lucille P. Markey Charitable Trust, and the Perot Family Foundation. M. C. S. is the recipient of a graduate fellowship from Fundacao Calouste Gulbenkian of Portugal and a Fulbright Scholarship. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USG Section 1734 solely to indicate this fact.
PY - 1992/9/18
Y1 - 1992/9/18
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.
AB - 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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U2 - 10.1016/0092-8674(92)90253-9
DO - 10.1016/0092-8674(92)90253-9
M3 - Article
C2 - 1525821
AN - SCOPUS:0026800719
SN - 0092-8674
VL - 70
SP - 1049
EP - 1057
JO - Cell
JF - Cell
IS - 6
ER -