MOLECULAR MECHANISM OF MEMBRANE-PROTEIN INTEGRATION INTO THE ENDOPLASMIC-RETICULUM

As proteins are integrated into the membrane of the endoplasmic reticu lum, some hydrophilic polypeptide segments are transported through the translocation channel, others remain in the cytosol, and hydrophobic transmembrane sequences are released into the lipid phase. We have add ressed the molecular mechanism by which these events occur. We demonst rate that both the lumenal and the cytosolic domains of a membrane pro tein are synthesized while the ribosome is membrane bound, so that eve n cytosolic domains come in contact with the translocation channel. We also find that, before translation of the protein is terminated, tran smembrane sequences can laterally exit the translocation channel and e nter the lipid environment. These results have significant implication s for the folding and assembly of membrane proteins.