The hydrophobic core of the Sec61 translocon defines the hydrophobicity threshold for membrane integration.
The Sec61 translocon mediates the translocation of proteins across the endoplasmic reticulum membrane and the lateral integration of transmembrane segments into the lipid bilayer. The structure of the idle translocon is closed by a lumenal plug domain and a hydrophobic constriction ring. To test the function of the apolar constriction, we have mutated all six ring residues of yeast Sec61p to more hydrophilic, bulky, or even charged amino acids (alanines, glycines, serines, tryptophans, lysines, or aspartates). The translocon was found to be surprisingly tolerant even to the charge mutations in the constriction ring, because growth and translocation efficiency were not drastically affected. Most interestingly, ring mutants were found to affect the integration of hydrophobic sequences into the lipid bilayer, indicating that the translocon does not simply catalyze the partitioning of potential transmembrane segments between an aqueous environment and the lipid bilayer but that it also plays an active role in setting the hydrophobicity threshold for membrane integration.
Junne
Tina
T
Biozentrum, University of Basel, Basel, Switzerland.
Kocik
Lucyna
L
Spiess
Martin
M
D000596:Amino Acids / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D022082:Cellular Structures / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism*; D018870:Endoplasmic Reticulum, Rough / Q000235:genetics / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000032:analysis / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism
D000596:Amino Acids; D008051:Lipid Bilayers; D001224:Aspartic Acid