ABSTRACT
Posttranslational geranylgeranylation of Rab GTPases is catalyzed by Rab geranylgeranyltransferase (RabGGTase), which consists of a catalytic alpha/beta heterodimer and an accessory Rab escort protein (REP). The crystal structure of isoprenoid-bound RabGGTase complexed to REP-1 has been solved to 2.7 A resolution. The complex interface buries a surprisingly small surface area of ca. 680 A and is unexpectedly formed by helices 8, 10, and 12 of the RabGGTase alpha subunit and helices D and E of REP-1. We demonstrate that the affinity of RabGGTase for REP-1 is allosterically regulated by phosphoisoprenoid via a long-range trans-domain signal transduction event. Comparing the structure of REP-1 with the closely related RabGDI, we conclude that the specificity of the REP:RabGGTase interaction is defined by differently positioned phenylalanine residues conserved in the REP and GDI subfamilies.
