Atopological Model for Hepatitis B Surface Antigen

Abstract

A model of hepatitis B surface antigen has been derived, based on extensive sequence analysis and biochemical data. The surface antigen sequences of the human, woodchuck, ground squirrel and duck hepadnaviruses were examined using hydrophobicity, hydrophobic moments, flexibility and secondary structure prediction. The helix phase diagram, which is a modified version of Eisenberg’s hydrophobic moment plots and which specifically addresses the problem of transmembrane helices, was used to examine the predicted helices. In this model four transmembrane helices are predicted. The N and C termini and the second hydrophilic region, which bears the major B-cell antigenic determinants, are external. It is suggested that the transmembrane helices may pack to form a channel through the membrane and may also be involved in the mechanisms of cell entry. A significant difference between the duck hepadnavirus and the mammalian HBsAg sequences was found, hence care must be taken when extrapolating data between the duck and the human surface antigen.

Identification of a new hepatitis B virus (HBV) genotype from Brazil that expresses HBV surface antigen subtype adw4

“…This suggests that these two sites of the molecule may interact with each other. A model presented recently proposed that these two sites are part of membrane-spanning a-helices A and D (Stirk et al, 1992). The amino acids G(145) (Ashton-Rickardt & Murray, 1989), K(122) and K(160) confirmed the results of the serotyping as adw4, on the nucleotide level.…”

Maturation of Recombinant Hepatitis B Virus Surface Antigen Particles

“…Eight out of a total of twelve tryptophan residues are located either in or near the transmembrane helices. 17 The fluorescence intensity at 332 nm decreases as a function of GdmSCN concentration, appearing to be in a biphasic mode. Therefore, the kinetics of unfolding of the protein complex could be followed by monitoring the decay of fluorescence intensity upon exposure to chaotropic environments, although the sensitivity of the intrinsic fluorescence change is limited at the concentration where the highly hydrophobic rHBsAg lipoprotein particles are soluble.…”

A ‘first loop’ linear epitope accessible on native hepatitis B surface antigen that persists in the face of ‘second loop’ immune escape

“…From denaturation and alkylation experiments (Imai et al, 1974), and work using linear and cyclical peptides , it is clear that the a determinant is a conformationally dependant epitope. Based on the model of HBsAg proposed by Stirk et al (1992), the a determinant is located on the extra-membranous loop that spans amino acid residues 101-159. This region contains eight cysteine residues and it is thought that disulphide bridges between the cysteines play a role in maintaining the correct conformation of the a determinant.…”