Multiple topogenic sequences determine the transmembrane orientation of the hepatitis B surface antigen.
To investigate the mechanism by which complex membrane proteins achieve their correct transmembrane orientation, we examined in detail the hepatitis B surface antigen for sequences which determine its membrane topology. The results demonstrated the presence of at least two kinds of topogenic elements: an N-terminal uncleaved signal sequence and an internal element containing both signal and stop-transfer function. Fusion of reporter groups to either end of the protein suggested that both termini are translocated across the membrane bilayer. We propose that this topology is generated by the conjoint action of both elements and involves a specifically oriented membrane insertion event mediated by the internal sequence. The functional properties of each element can be instructively compared with those of simpler membrane proteins and may provide insight into the generation of other complex protein topologies.
Eble
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BE
Department of Microbiology and Immunology, University of California Medical Center, San Francisco 94143.
MacRae
D R
DR
Lingappa
V R
VR
Ganem
D
D
D001692:Biological Transport; D004252:DNA Mutational Analysis; D005914:Globins / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D008565:Membrane Proteins; D008861:Microsomes / Q000378:metabolism; D011487:Protein Conformation; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship
D006514:Hepatitis B Surface Antigens; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D005914:Globins