2ypv

Crystal structure of the Meningococcal vaccine antigen factor H binding protein in complex with a bactericidal antibody

spinqualitylabelsall models 2ypv, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ypv is a 3 chain structure with sequence from Mus musculus and Neisseria meningitidis MC58. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FHBP_NEIMB A bacterial surface lipoprotein that binds host (human) complement factor H (fH, gene CFH), binding contributes to the avoidance of complement-mediated lysis by N.meningitidis. Binding of fH to the bacteria surface is independent of bacterial sialic acid moieties (PubMed:16751403). fH binding affinity is high enough that it may sequester plasma fH, depleting its circulating levels and de-regulating complement in the host (Probable). This protein induces high levels of bactericidal antibodies in mice (PubMed:12642606, PubMed:15039331, PubMed:15664958, PubMed:21753121, PubMed:23133374). Publication Abstract from PubMed Mapping of epitopes recognized by functional monoclonal antibodies (mAbs) is essential for understanding the nature of immune responses and designing improved vaccines, therapeutics, and diagnostics. In recent years, identification of B-cell epitopes targeted by neutralizing antibodies has facilitated the design of peptide-based vaccines against highly variable pathogens like HIV, respiratory syncytial virus, and Helicobacter pylori; however, none of these products has yet progressed into clinical stages. Linear epitopes identified by conventional mapping techniques only partially reflect the immunogenic properties of the epitope in its natural conformation, thus limiting the success of this approach. To investigate antigen-antibody interactions and assess the potential of the most common epitope mapping techniques, we generated a series of mAbs against factor H binding protein (fHbp), a key virulence factor and vaccine antigen of Neisseria meningitidis. The interaction of fHbp with the bactericidal mAb 12C1 was studied by various epitope mapping methods. Although a 12-residue epitope in the C terminus of fHbp was identified by both Peptide Scanning and Phage Display Library screening, other approaches, such as hydrogen/deuterium exchange mass spectrometry (MS) and X-ray crystallography, showed that mAb 12C1 occupies an area of approximately 1,000 A(2) on fHbp, including >20 fHbp residues distributed on both N- and C-terminal domains. Collectively, these data show that linear epitope mapping techniques provide useful but incomplete descriptions of B-cell epitopes, indicating that increased efforts to fully characterize antigen-antibody interfaces are required to understand and design effective immunogens. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen.,Malito E, Faleri A, Lo Surdo P, Veggi D, Maruggi G, Grassi E, Cartocci E, Bertoldi I, Genovese A, Santini L, Romagnoli G, Borgogni E, Brier S, Lo Passo C, Domina M, Castellino F, Felici F, van der Veen S, Johnson S, Lea SM, Tang CM, Pizza M, Savino S, Norais N, Rappuoli R, Bottomley MJ, Masignani V Proc Natl Acad Sci U S A. 2013 Feb 8. PMID:23396847 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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