2ypv

From Proteopedia

(Difference between revisions)

Current revision

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

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:
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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Masignani V, Comanducci M, Giuliani MM, Bambini S, Adu-Bobie J, Arico B, Brunelli B, Pieri A, Santini L, Savino S, Serruto D, Litt D, Kroll S, Welsch JA, Granoff DM, Rappuoli R, Pizza M. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med. 2003 Mar 17;197(6):789-99. PMID:12642606 doi:10.1084/jem.20021911
↑ Fletcher LD, Bernfield L, Barniak V, Farley JE, Howell A, Knauf M, Ooi P, Smith RP, Weise P, Wetherell M, Xie X, Zagursky R, Zhang Y, Zlotnick GW. Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun. 2004 Apr;72(4):2088-100. PMID:15039331 doi:10.1128/IAI.72.4.2088-2100.2004
↑ Giuliani MM, Santini L, Brunelli B, Biolchi A, Aricò B, Di Marcello F, Cartocci E, Comanducci M, Masignani V, Lozzi L, Savino S, Scarselli M, Rappuoli R, Pizza M. The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies. Infect Immun. 2005 Feb;73(2):1151-60. PMID:15664958 doi:10.1128/IAI.73.2.1151-1160.2005
↑ Schneider MC, Exley RM, Chan H, Feavers I, Kang YH, Sim RB, Tang CM. Functional significance of factor H binding to Neisseria meningitidis. J Immunol. 2006 Jun 15;176(12):7566-75. PMID:16751403 doi:10.4049/jimmunol.176.12.7566
↑ Scarselli M, Arico B, Brunelli B, Savino S, Di Marcello F, Palumbo E, Veggi D, Ciucchi L, Cartocci E, Bottomley MJ, Malito E, Lo Surdo P, Comanducci M, Giuliani MM, Cantini F, Dragonetti S, Colaprico A, Doro F, Giannetti P, Pallaoro M, Brogioni B, Tontini M, Hilleringmann M, Nardi-Dei V, Banci L, Pizza M, Rappuoli R. Rational design of a meningococcal antigen inducing broad protective immunity. Sci Transl Med. 2011 Jul 13;3(91):91ra62. PMID:21753121 doi:10.1126/scitranslmed.3002234
↑ Johnson S, Tan L, van der Veen S, Caesar J, Goicoechea De Jorge E, Harding RJ, Bai X, Exley RM, Ward PN, Ruivo N, Trivedi K, Cumber E, Jones R, Newham L, Staunton D, Ufret-Vincenty R, Borrow R, Pickering MC, Lea SM, Tang CM. Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules. PLoS Pathog. 2012 Oct;8(10):e1002981. doi: 10.1371/journal.ppat.1002981. Epub, 2012 Oct 25. PMID:23133374 doi:http://dx.doi.org/10.1371/journal.ppat.1002981
↑ Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769
↑ 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. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen. Proc Natl Acad Sci U S A. 2013 Feb 8. PMID:23396847 doi:http://dx.doi.org/10.1073/pnas.1222845110

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ypv"

@@ Line 3: / Line 3: @@
 <StructureSection load='2ypv' size='340' side='right'caption='[[2ypv]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ypv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Neimb Neimb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YPV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ypv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Neisseria_meningitidis_MC58 Neisseria meningitidis MC58]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YPV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ypv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypv OCA], [https://pdbe.org/2ypv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ypv RCSB], [https://www.ebi.ac.uk/pdbsum/2ypv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ypv ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/FHBP_NEIMB 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).<ref>PMID:12642606</ref> <ref>PMID:15039331</ref> <ref>PMID:15664958</ref> <ref>PMID:16751403</ref> <ref>PMID:21753121</ref> <ref>PMID:23133374</ref> <ref>PMID:19225461</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 25: @@
 [[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Neimb]]
+[[Category: Neisseria meningitidis MC58]]
-[[Category: Bottomley, M J]]
+[[Category: Bottomley MJ]]
-[[Category: Malito, E]]
+[[Category: Malito E]]
-[[Category: Veggi, D]]
+[[Category: Veggi D]]
-[[Category: Epitope mapping]]
-[[Category: Immune system]]
-[[Category: Mab]]
-[[Category: Monoclonal antibody]]
-[[Category: Vaccine]]

2ypv

From Proteopedia

Current revision

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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