SEC61p is the channel-forming subunit of the heterotrimeric SEC61 complex that mediates co-translational protein import into the endoplasmic reticulum (ER). In yeast, proteins can also be post-translationally translocated by the hetero-heptameric Sec complex, composed of the SEC61 and the SEC63 complexes. The SEC61 channel is also a candidate for the dislocation channel for misfolded proteins from the ER to the cytosol during ER-associated degradation (ERAD). The structure of the SEC61 complex is highly conserved, but the roles of its N-terminal acetylation and its amphipathic N-terminal helix are unknown so far. To gain insight into the function of the SEC61p N-terminus, we mutated its N-acetylation site, deleted its amphipathic helix, or both the helix and the N-acetylation site. Mutation of the N-acetylation site on its own had no effect on protein import into the ER in intact cells, but resulted in an ERAD defect. Yeast expressing SEC61 without the N-terminal amphipathic helix displayed severe growth defects and had profound defects in post-translational protein import into the ER. Nevertheless the formation of the hetero-heptameric Sec complex was not affected. Instead, the lack of the N-terminal amphipathic helix compromised the integrity of the heterotrimeric SEC61 complex. We conclude that the N-terminal helix of SEC61p is required for post-translational protein import into the ER and SEC61 complex stability, whereas N-terminal acetylation of SEC61p plays a role in ERAD.

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Journal Article | Research Support, Non-U.S. Gov't

Authors

Elia F, Yadhanapudi L, Tretter T, Römisch K

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