cDNA cloning of component A of rat Rab geranylgeranyl transferase confirms identity of the protein with the human choroideremia gene product and its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI), which binds prenylated Rabs. In biochemical assays we demonstrate that component A binds unprenylated Rab1A, presents it to the catalytic component B, and remains bound to it after the geranylgeranyl transfer reaction. In the absence of detergents, the reaction terminates when all of component A is occupied with prenylated Rab. Detergents allow multiple rounds of catalysis, apparently by dissociating the component A-Rab complex and thus allowing recycling of component A. Within the cell, component A may be regenerated by transferring its prenylated Rab to a protein acceptor, such as Rab3A GDI. In view of its function in escorting Rab proteins during and presumably after the prenyl transfer reaction, we propose to rename component A as Rab escort protein (REP). A genetic defect in REP underlies human choroideremia, a disease of retinal degeneration.
|Number of pages||9|
|State||Published - Jun 18 1993|
Bibliographical noteFunding Information:
We thank Thomas Siidhof for helpful comments; Richard Gibson and Veronica Martinez for excellent technical assistance; and Jeff Cormier for DNA sequencing. This research was supported by research grants from the National Institutes of Health (HL20946) and the Perot Family Foundation. D. A. A. is the recipient of a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Rs-search; M. C. S. is the recipient of a Fulbright Scholarship; S. A. A. is supported by Medical Scientists Training Grant GM06014. F. P. M. C. is the recipient of a sabbatical fellowship from the Royal Netherlands Academy of Arts and Sciences; his permanent address is at the Department of Human Genetics, University Hospital Nijmegen, 6506 HB Nijmegen, The Netherlands.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)