cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein

Douglas A. Andres, Miguel C. Seabra, Michael S. Brown, Scott A. Armstrong, Tor E. Smeland, Frans P M Cremers, Joseph L. Goldstein

Research output: Contribution to journalArticlepeer-review

303 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1091-1099
Number of pages9
JournalCell
Volume73
Issue number6
DOIs
StatePublished - Jun 18 1993

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein'. Together they form a unique fingerprint.

Cite this