Molecular evolution of the Rab-escort-protein/guanine-nucleotide-dissociation-inhibitor superfamily.
Prenylation of Rab GTPases regulating vesicle traffic by Rab geranylgeranyltransferase (RabGGTase) requires a complex formed by the association of newly synthesized Rab proteins with Rab-escort-protein (REP), the choroideremia-gene-product that is mutated in disease, leading to loss of vision. After delivery to the membrane by the REP-Rab complex, subsequent recycling to the cytosol requires the REP-related guanine-nucleotide-dissociation-inhibitor (GDI). Although REP and GDI share common Rab-binding properties, GDI cannot assist in Rab prenylation and REP cannot retrieve Rab proteins from the membranes. We have now isolated REP mutant proteins that are able to partially function as both REP and GDI. These results provide molecular insight into the functional and evolutionary organization of the REP/GDI superfamily.
Alory
Christelle
C
Departments of Cell and Molecular Biology and The Institute for Childhood and Neglected Diseases, The Scripps Research Institute, La Jolla, California 92130, USA. welbach@scripps.edu
Balch
William E
WE
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D008961:Models, Structural; D009154:Mutation; D011485:Protein Binding; D017368:Protein Prenylation / Q000502:physiology; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D020730:Guanine Nucleotide Dissociation Inhibitors; D019883:Alkyl and Aryl Transferases; C075607:Rab geranylgeranyltransferase; D020691:rab GTP-Binding Proteins