DSS4-1 is a dominant suppressor of sec4-8 that encodes a nucleotide exchange protein that aids Sec4p function.

The protein Sec4p plays an essential role at the final stage of the yeast secretory pathway and belongs to the ras superfamily of GTP-binding proteins, more specifically to a branch that includes Ypt1p in Saccharomyces cerevisiae and rab proteins in mammalian cells. GTP-binding proteins change conformation depending on whether GTP or GDP is bound and can thus act as a regulatory switch. The protein remains in its inactive, GDP-bound form until exchange of GTP for GDP allows it to stimulate a downstream effector. This interaction is curtailed by GTP hydrolysis. The rates of nucleotide exchange and GTP hydrolysis can be regulated by interaction with accessory proteins. Although GDP dissociation stimulators (GDS) have been identified that act on members of the ras and rho branches of the superfamily, less is known regarding GDSs that act on members of the Sec4/Ypt1/Rab subgroup. A preliminary characterization of a Rab3A GDP dissociation stimulating activity has been presented. We report here the use of suppressor analysis to clone a gene, dss4, encoding a 17K protein that aids Sec4p action in vivo by functioning as a GDP dissociation stimulator.