Bet2p and Mad2p are components of a prenyltransferase that adds geranylgeranyl onto Ypt1p and Sec4p

Abstract

THREE different prenyltransferases have been identified in yeast and higher cells1–6, the farnesyltransferase and the type I and type II geranylgeranyltransferases (GGTase). The farnesyltransferase and GGTase-I modify peptides in vitro with the CAAX (C, Cys; A, aliphatic residue; X, terminal amino acid) consensus motif2,7. These enzymes are heterodimers that have different β-subunits and a shared α-subunit8. In yeast, the RAM2 gene encodes this α-subunit9. RAM2 is also homologous to MAD2, a yeast gene whose product has been implicated in the feedback control of mitosis10,11. We have shown that Bet2p is a component of the yeast GGTase-II (refs 6,12) that geranylgeranylates Yptlp, a small GTP-binding protein that mediates transport from the endoplasmic reticulum to the Golgi complex13–15. Here we report that Mad2p is a component of this enzyme. Bet2p forms a complex with Mad2p that appears to bind geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. The efficient transfer of geranylgeranyl onto small GTP-binding proteins requires the presence of an additional activity.