title: Crystal structure of an Fab fragment in complex with a meningococcal serosubtype antigen and a protein G domain.
abstract: Many pathogens present highly variable surface proteins to their host as a means of evading immune responses. The structure of a peptide antigen corresponding to the subtype P1.7 variant of the porin PorA from the human pathogen Neisseria meningitidis was determined by solution of the X-ray crystal structure of the ternary complex of the peptide (ANGGASGQVK) in complex with a Fab fragment and a domain from streptococcal protein G to 1.95 A resolution. The peptide adopted a beta-hairpin structure with a type I beta-turn between residues Gly4P and Gly7P, the conformation of the peptide being further stabilised by a pair of hydrogen bonds from the side-chain of Asn2P to main-chain atoms in Val9P. The antigen binding site within the Fab formed a distinct crevice lined by a high proportion of apolar amino acids. Recognition was supplemented by hydrogen bonds from heavy chain residues Thr50H, Asp95H, Leu97H and Tyr100H to main-chain and side-chain atoms in the peptide. Complementarity-determining region (CDR) 3 of the heavy chain was responsible for approximately 50 % of the buried surface area formed by peptide-Fab binding, with the remainder made up from CDRs 1 and 3 of the light chain and CDRs 1 and 2 of the heavy chain. Knowledge of the structures of variable surface antigens such as PorA is an essential prerequisite to a molecular understanding of antigenic variation and its implications for vaccine design.
authors.affiliation: Department of Biomolecular Sciences, UMIST, Manchester, M60 1QD, UK. Jeremy.Derrick@umist.ac.uk
authors.forename: J P
authors.initials: JP
authors.lastname: Derrick
authors.forename: M C
authors.initials: MC
authors.lastname: Maiden
authors.forename: I M
authors.initials: IM
authors.lastname: Feavers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000276:immunology; D018272:Porins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; C029152:G-substrate; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; C121421:MOPC21 monoclonal antibody; D009419:Nerve Tissue Proteins; D018272:Porins; C057699:porin protein, Neisseria