2mpa
From Proteopedia
(New page: 200px<br /> <applet load="2mpa" size="450" color="white" frame="true" align="right" spinBox="true" caption="2mpa, resolution 2.6Å" /> '''BACTERICIDAL ANTIBOD...) |
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| - | [[Image:2mpa.gif|left|200px]]<br /> | + | [[Image:2mpa.gif|left|200px]]<br /><applet load="2mpa" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2mpa" size=" | + | |
caption="2mpa, resolution 2.6Å" /> | caption="2mpa, resolution 2.6Å" /> | ||
'''BACTERICIDAL ANTIBODY AGAINST NEISSERIA MENINGITIDIS'''<br /> | '''BACTERICIDAL ANTIBODY AGAINST NEISSERIA MENINGITIDIS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Class 1 outer membrane protein PorA of Neisseria meningitidis is a vaccine | + | Class 1 outer membrane protein PorA of Neisseria meningitidis is a vaccine candidate against bacterial meningitis. Antibodies against PorA are able to induce complement-mediated bacterial killing and thereby play an important role in protection against meningococcal disease. Bactericidal antibodies are all directed against variable regions VR1 and VR2 of the PorA sequence, corresponding to loops 1 and 4 of a two-dimensional topology model of the porin with eight extracellular loops. We have determined the crystal structure to 2.6 A resolution of the Fab fragment of bactericidal antibody MN12H2 against meningococcal PorA in complex with a linear fluorescein-conjugated peptide TKDTNNNL derived from the VR2 sequence of sero-subtype P1.7,16 (residues 180-187) from meningococcal strain H44/76. The peptide folds deeply into the binding cavity of the Fab molecule in a type I beta-turn, with the minimal P1.16 epitope DTNNN virtually completely buried. The structure reveals H-bonds and van der Waals interactions with all minimal epitope residues and one essential salt bridge between Asp-182 of the peptide and His-31 of the MN12H2 light chain. The key components of the recognition of PorA epitope P1.16 by bactericidal antibody MN12H2 correspond well with available thermodynamic data from binding studies. Furthermore, they indicate the structural basis of an increased endemic incidence of infection by group B meningococci in England and Wales since 1981 associated with the occurrence of an Neisseria meningitidis escape mutant (strain-MC58). The observed three-dimensional conformation of the peptide provides a rationale for the development of a synthetic peptide vaccine against meningococcal disease. |
==About this Structure== | ==About this Structure== | ||
| - | 2MPA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2MPA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=CD:'>CD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MPA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Elsen, J | + | [[Category: Elsen, J M.H Van Den.]] |
[[Category: Gros, P.]] | [[Category: Gros, P.]] | ||
| - | [[Category: Herron, J | + | [[Category: Herron, J N.]] |
[[Category: Kroon, J.]] | [[Category: Kroon, J.]] | ||
[[Category: CD]] | [[Category: CD]] | ||
[[Category: bactericidal antibody]] | [[Category: bactericidal antibody]] | ||
[[Category: complex (immunoglobulin/peptide)]] | [[Category: complex (immunoglobulin/peptide)]] | ||
| - | [[Category: epitope p1 | + | [[Category: epitope p1 16 of pora from neisseria meningitidis]] |
[[Category: murine immunoglobulin igg2a kappa]] | [[Category: murine immunoglobulin igg2a kappa]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:07:52 2008'' |
Revision as of 16:07, 21 February 2008
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BACTERICIDAL ANTIBODY AGAINST NEISSERIA MENINGITIDIS
Overview
Class 1 outer membrane protein PorA of Neisseria meningitidis is a vaccine candidate against bacterial meningitis. Antibodies against PorA are able to induce complement-mediated bacterial killing and thereby play an important role in protection against meningococcal disease. Bactericidal antibodies are all directed against variable regions VR1 and VR2 of the PorA sequence, corresponding to loops 1 and 4 of a two-dimensional topology model of the porin with eight extracellular loops. We have determined the crystal structure to 2.6 A resolution of the Fab fragment of bactericidal antibody MN12H2 against meningococcal PorA in complex with a linear fluorescein-conjugated peptide TKDTNNNL derived from the VR2 sequence of sero-subtype P1.7,16 (residues 180-187) from meningococcal strain H44/76. The peptide folds deeply into the binding cavity of the Fab molecule in a type I beta-turn, with the minimal P1.16 epitope DTNNN virtually completely buried. The structure reveals H-bonds and van der Waals interactions with all minimal epitope residues and one essential salt bridge between Asp-182 of the peptide and His-31 of the MN12H2 light chain. The key components of the recognition of PorA epitope P1.16 by bactericidal antibody MN12H2 correspond well with available thermodynamic data from binding studies. Furthermore, they indicate the structural basis of an increased endemic incidence of infection by group B meningococci in England and Wales since 1981 associated with the occurrence of an Neisseria meningitidis escape mutant (strain-MC58). The observed three-dimensional conformation of the peptide provides a rationale for the development of a synthetic peptide vaccine against meningococcal disease.
About this Structure
2MPA is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Bactericidal antibody recognition of a PorA epitope of Neisseria meningitidis: crystal structure of a Fab fragment in complex with a fluorescein-conjugated peptide., van den Elsen JM, Herron JN, Hoogerhout P, Poolman JT, Boel E, Logtenberg T, Wilting J, Crommelin DJ, Kroon J, Gros P, Proteins. 1997 Sep;29(1):113-25. PMID:9294871
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