Abstract
The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis. Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the evolutionarily conserved Sec61 complex, a heterotrimeric channel that comprises the Sec61p/Sec61α, Sss1p/Sec61γ, and Sbh1p/Sec61β subunits. In addition to forming a protein-conducting channel, the Sec61 complex also functions to maintain the ER permeability barrier, preventing the mass free flow of essential ER-enriched molecules and ions. Loss in Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61γ C terminus is juxtaposed to the key gating module of Sec61p/Sec61α, and we hypothesize it is important for gating the ER translocon. The ER stress response was found to be constitutively induced in two temperature-sensitive sss1 mutants (sss1ts ) that are still proficient to conduct ER translocation. A screen to identify intergenic mutations that allow for sss1ts cells to grow at 37 °C suggests the ER permeability barrier to be compromised in these mutants. We propose the extreme C terminus of Sss1p/Sec61γ is an essential component of the gating module of the ER translocase and is required to maintain the ER permeability barrier.
Highlights
The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis
Cotranslational translocation is initiated upon recognition of the hydrophobic signal sequence by the signal recognition particle (SRP) as it emerges from the ribosome [2,3,4,5,6]
Eukaryotes encode for a second ER translocase which contains Ssh1p/Sec61␣2, Sss1p/Sec61␥, and Sbh2p/Sec61 (Fig. 1A)
Summary
The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis. Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the evolutionarily conserved Sec complex, a heterotrimeric channel that comprises the Sec61p/Sec61␣, Sss1p/Sec61␥, and Sbh1p/Sec61 subunits. Upon resumption of translation the nascent chain moves through the pore and into the lumen of the ER where cleavable signal sequences are processed by the signal peptidase complex (9 –12). Smaller proteins or those containing a moderately hydrophobic signal sequence are completely synthesized in the cytoplasm and translocated posttranslationally [3, 13]. Upon association with the SEC complex, chaperones are released and the signal peptide of the secretory precursor is inserted into the translocation channel after which translocation is facilitated by Kar2p (BiP in mammals) [16, 21]
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