Structure of the Fab fragment from F124, a monoclonal antibody specific for hepatitis B surface antigen

The crystal structure of the Fab fragment from the monoclonal anti-preS2 an tibody F124 (IgG1,kappa) has been solved by molecular replacement and refin ed at 3.0 Angstrom resolution. The Fab crystallizes with two independent mo lecules in the asymmetric unit. F124 recognizes an epitope contained within the preS2 segment between residues 120 and 132 of the surface antigen of h epatitis B virus. The antibody shows a high affinity for the glycan N-linke d to Asn123, but it also crossreacts with the non-glycosylated peptide frag ment 120-132. Although crystallization was performed in the presence of an eightfold excess of the cross-reactive peptide, no evidence for the ligand was found in the antigen-binding site, which is close to a neighbouring mol ecule in the crystal lattice. The antigen-binding site has a groove-like to pology which is modulated with pocket-like cavities. It is characterized by a large number of tyrosine and aspartate residues. The importance of germl ine mutations at the binding site is discussed.