Isoform-selective Oligomer Formation of Saccharomyces cerevisiae p24 Family Proteins

p24 family proteins are evolutionarily conserved transmembrane proteins involved in the early secretory pathway. Saccharomyces cerevisiae has 8 known p24 proteins that are classified into four subfamilies (p24, -, -, and -). Emp24 and Erv25 are the sole members of p24 and -, respectively, and deletion of either destabilizes the remaining p24 proteins, resulting in p24 null phenotype (p24). We studied genetic and physical interactions of p24 (Erp1, -5, and -6) and (Erp2, -3, and -4). Deletion of the major p24 (Erp1) partially inhibited p24 activity as reported previously. A second mutation in either Erp5 or Erp6 aggravated the erp1 phenotype, and the triple mutation gave a full p24 phenotype. Similar genetic interactions were observed among the major p24 (Erp2) and the other two members. All the p24/ isoforms interacted with both p24 and -. Interaction between p24 and - was isoform-selective, and five major / pairs were detected. These results suggest that the yeast p24 proteins form functionally redundant complexes. We also identified Rrt6 as a novel p24 isoform. Rrt6 shows only limited sequence identity (approximate to 15%) to known p24 proteins but was found to have structural properties characteristic of p24. Rrt6 was induced when cells were grown on glycerol and form an additional complex with Erp3, Erp5, and Emp24. This complex was mainly localized to the Golgi, whereas the p24 complex containing Erv25, instead of Rrt6 but otherwise with the same isoform composition, was found mostly in the ER.