An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles.
Bottom Line: Heterologous sequences have been successfully inserted at both amino and carboxy termini as well as internally at the major immunodominant epitope.The insert was seen to form a trimeric spike on the capsid surface that was poorly resolved, most likely owing to it being flexible.We hypothesise that the capacity of N-terminal inserts to form trimers may have application in the development of multivalent vaccines to trimeric antigens.
Affiliation: MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, Scotland, UK.Show MeSH
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Mentions: To further understand the structure of the N-terminal extension in His-β-L HBcAg VLPs we used MOE to model the tertiary structure of the protein. The models judged to be the best predicted that the extension would contain an unstructured region followed by an alpha helix located between residues Met12-Asp28, Ser4-Asp24 or His10-Asp28 in the top 3 models. Thus in two models the alpha helix was C-terminal to the polyhistidine tract while the remaining model incorporated the 6HIS motif into the helix. The length of the alpha helix varied in the different models ranging between 24 and 29 Å. Upon comparison with our T = 3 structure the models did not match the reconstructed density well, the orientation of the N-terminal extension varied widely between predicted structures and in all cases clashed with symmetry related protomers (Fig. 5). As the reconstructed density for the N-terminal extension was poorly resolved, no attempt was made to refine the models by flexible fitting.
Affiliation: MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, Scotland, UK.