Solution conformation of an immunodominant epitope in the hepatitis B virus preS2 surface antigen

We have determined the solution conformation of the major B cell epitope (residues 123–145, adrl23 hereafter) in the preS2 region of hepatitis B virus known to be associated with infection neutralization. The adrl23 shows an “L” shaped helix-turn-helix topology with two β-turns formed by residues Ala130-Asp133 and Asp133-Val136 intervening the N- and C-terminal helices. The N-terminal α-helix consists of residues Ser124-Gln129 whereas the C-terminal 310 helix is formed by residues Val136-Tyr140. The β-turns overlap partially with the putative “conformational” epitope. The overall topology of adrl23 is primarily maintained by hydrophobic interactions involving Phe127, Leu131, Leu132, Val136, and Tyr140 that are clustered on one side of the molecule. An additional hydrophobic stabilization comes from Phe141 that is buried inside the concave side of the molecule. A network of hydrogen bonds formed among Thr125, His128, and Arg137 further contribute to the “boomerang-shaped” architecture of adrl23. The N-terminus of adrl23 is immobile due to a hydrogen bond between the N-terminal amide proton of Asn123 and the hydroxyl oxygen of Thr126. The side chains of Asp133, Arg135, Val136, Leu139, and Tyr140 that were shown to be important for binding to a monoclonal antibody H8 mAb are surface exposed.