Sss1p, a small essential protein, is a subunit of the heterotrimeric Sec61 complex, also referred to as the translocon (1, reviewed in 6). The Sec61 complex forms a channel in the endoplasmic reticulum (ER) membrane and mediates translocation of secretory and membrane proteins into the ER and also retrograde transport of misfolded proteins to the cytoplasm for degradation (reviewed in 7 and 8). The other subunits of the Sec61 complex include Sec61p, the major subunit that contains ten transmembrane domains and forms the protein-conducting channel, and Sbh1p (9, 10, reviewed in 6). Sss1p is also a subunit of the structurally related trimeric Ssh1p complex, consisting of Ssh1p, Sbh2p, and Sss1p, that is thought to function exclusively in cotranslational translocation (2).

Proteins that are transported into or across the ER membrane are directed there by signal sequences or by transmembrane segments that interact with the translocation apparatus. In S. cerevisiae the Sec61 complex mediates both co- and posttranslational translocation (while the mammalian Sec61 complex functions primarily with the cotranslational pathway; 11). During cotranslational translocation, ribosomes synthesizing signal sequence-containing proteins are targeted to the translocon via the signal recognition particle (SRP), and the ribosomes bind directly to Sec61p such that protein biosynthesis and translocation are synchronous (12). Posttranslational translocation requires Sec62p, Sec63p, Sec66p, and Sec72p (comprising the Sec63 complex), as well as Kar2p, in place of SRP to facilitate interaction of the full-length polypeptide with the translocon via the signal sequence (13, 14).

Retrograde transport of misfolded proteins into the cytoplasm (also called dislocation) employs the Sec61 channel via interaction with the 19S proteasome regulatory particle (15). This interaction, which competes with the ribosome-Sec61p interaction, defines the Sec61 complex as the principal proteasome receptor in the ER membrane (15).

SSS1 (for Sec Sixty-one Suppressor) overexpression restores translocation in the sec61-3 temperature sensitive mutant (5, 16). Sss1p interacts physically with Sec61p in a region including the transmembrane segments TM6, TM7, and TM8 (amino acids L232-R406), and functions to stabilize the translocation channel (1, 16). In addition, Sss1p exhibits physical interactions with some of the oligosaccharyltransferase (OST) subunits and thus may facilitate binding of OST to the channel to promote efficient N-linked glycosylation of glycoproteins (3, 4). Sss1p is an integral membrane protein and its amino terminal half is exposed to the cytosol (1).

Sss1p is conserved among organisms and the human homolog, Sec61 gamma, functionally complements an sss1 null mutation in S. cerevisiae (17). Bacterial and archaeal Sss1p orthologs are referred to as SecE (17, reviewed in 6).

Last updated: 2007-11-09