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

Abstract

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 Ala 130-Asp 133 and Asp 133-Val 136 intervening the N- and C-terminal helices. The N-terminal α-helix consists of residues Ser 124-Gln 129 whereas the C-terminal 3 10 helix is formed by residues Val 136-Tyr 140. The β-turns overlap partially with the putative “conformational” epitope. The overall topology of adrl23 is primarily maintained by hydrophobic interactions involving Phe 127, Leu 131, Leu 132, Val 136, and Tyr 140 that are clustered on one side of the molecule. An additional hydrophobic stabilization comes from Phe 141 that is buried inside the concave side of the molecule. A network of hydrogen bonds formed among Thr 125, His 128, and Arg 137 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 Asn 123 and the hydroxyl oxygen of Thr 126. The side chains of Asp 133, Arg 135, Val 136, Leu 139, and Tyr 140 that were shown to be important for binding to a monoclonal antibody H8 mAb are surface exposed.