The N-terminal (pre-S2) domain of a hepatitis B virus surface glycoprotein is translocated across membranes by downstream signal sequences.
The coding region for the hepatitis B virus surface antigens contains three in-phase ATG codons which direct the synthesis of three related polypeptides. The 24-kilodalton major surface (or S) glycoprotein is initiated at the most distal ATG and is a transmembrane protein whose translocation across the bilayer is mediated by at least two uncleaved signal sequences. The product of the next upstream ATG is the 31-kilodalton pre-S2 protein, which contains 55 additional amino acids attached to the N terminus of the S protein. This pre-S2-specific domain is translocated into the endoplasmic reticulum. Using a coupled in vitro translation-translocation system, we showed that (i) the pre-S2 domain itself lacks functional signal sequence activity, (ii) its translocation across the endoplasmic reticulum membrane is mediated by downstream signals within the S domain, and (iii) the N-terminal signal sequence of the S protein can translocate upstream protein domains in the absence of other signals. The hepatitis B virus pre-S2 protein is an example of a natural protein which displays upstream domain translocation, a phenomenon whose existence was originally inferred from the behavior of synthetic fusion proteins in vitro.
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Department of Microbiology, University of California Medical Center, San Francisco 94143-0502.
Lingappa
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Ganem
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D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005814:Genes, Viral; D006031:Glycosylation; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D008861:Microsomes / Q000378:metabolism; D008970:Molecular Weight; D010957:Plasmids; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D006514:Hepatitis B Surface Antigens; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D012333:RNA, Messenger