biostudies-literatureDemirci ESwiss National Science Foundation18856-61https://www.ebi.ac.uk/biostudies/studies/S-EPMC3839696biostudies-literatureUnknown110(47)The Sec61 translocon forms a pore to translocate polypeptide sequences across the membrane and offers a lateral gate for membrane integration of hydrophobic (H) segments. A central constriction of six apolar residues has been shown to form a seal, but also to determine the hydrophobicity threshold for membrane integration: Mutation of these residues in yeast Sec61p to glycines, serines, aspartates, or lysines lowered the hydrophobicity required for integration; mutation to alanines increased it. Whereas four leucines distributed in an oligo-alanine H segment were sufficient for 50% integration, we now find four leucines in the N-terminal half of the H segment to produce significantly more integration than in the C-terminal half, suggesting functional asymmetry within the translocon. ScanniProceedings of the National Academy of Sciences of the United States of AmericaFunctional asymmetry within the Sec61p translocon.PMC3839696144111139205Baday SBerneche SJunne TSpiess MDemirci EfalseFunctional asymmetry within the Sec61p translocon.The Sec61 translocon forms a pore to translocate polypeptide sequences across the membrane and offers a lateral gate for membrane integration of hydrophobic (H) segments. A central constriction of six apolar residues has been shown to form a seal, but also to determine the hydrophobicity threshold for membrane integration: Mutation of these residues in yeast Sec61p to glycines, serines, aspartates, or lysines lowered the hydrophobicity required for integration; mutation to alanines increased it. Whereas four leucines distributed in an oligo-alanine H segment were sufficient for 50% integration, we now find four leucines in the N-terminal half of the H segment to produce significantly more integration than in the C-terminal half, suggesting functional asymmetry within the translocon. Scanni2013-01-01T00:00:00Z2013 Nov2026-05-02T01:18:48.768Z2019-03-27T03:09:14ZS-EPMC38396962419104610.1073/pnas.1318432110