9513819 Fang In eukaryotic organisms, proteins that are destined for secretion contain an amino-terminal signal peptide, a short sequence of amino acids that direct co-translational translocation of the nascent protein across the membrane of the endoplasmic reticulum (ER). Once this signal sequence completes its task of leading the nascent protein across the membrane, it is proteolytically removed by the action of a signal peptidase on the lumenal side of the ER. The signal peptidase complex is a multi-subunit enzyme complex in the endoplasmic reticulum. This small one-year award will support initiation of research activities aimed toward functional characterizations of two newly-identified genes involved in the activity of the yeast (Saccharomyces cerevisiae) signal peptidase complex (SPC): SPC3, an essential gene which encodes the 25 kD subunit of yeast SPC; and SPC4, a gene isolated as a high-copy suppressor of a temperature-sensitive mutant of Sec11, the gene encoding the 18kD subunit. The studies of SPC3 will include phenotypic analyses of temperature-sensitive mutants after shift to the non-permissive temperature, and biochemical analyses of the interactions of the gene product with other proteins using epitope tagging. The studies of SPC4 will include phenotypic analyses of mutations in this gene. ***
