The Sec61p complex mediates the integration of a membrane protein by allowing lipid partitioning of the transmembrane domain.
We have investigated how the transmembrane (TM) domain of a membrane protein is cotranslationally integrated into the endoplasmic reticulum. We demonstrate that the Sec61p channel allows the TM domain to bypass the barrier posed by the polar head groups of the lipid bilayer and come into contact with the hydrophobic interior of the membrane. Together with the TRAM protein, Sec61p provides a site in the membrane, at the interface of channel and lipid, through which a TM domain can dynamically equilibrate between the lipid and aqueous phases, depending on the hydrophobicity of the TM domain and the length of the polypeptide segment tethering it to the ribosome. Our results suggest a unifying, lipid-partitioning model which can explain the general behavior of hydrophobic topogenic sequences.
Heinrich
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Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mothes
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Brunner
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Rapoport
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TA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003432:Cross-Linking Reagents; D004285:Dogs; D019286:Endopeptidase K / Q000378:metabolism; D006031:Glycosylation; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D000069816:SEC Translocation Channels
D003432:Cross-Linking Reagents; D008563:Membrane Lipids; D008565:Membrane Proteins; D000069816:SEC Translocation Channels; D019286:Endopeptidase K