PDBsum entry 2mpa

Immune system

PDB id

2mpa

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Contents

			Protein chains

					219 a.a. *


					224 a.a. *

			Ligands

					THC-LYS-ASP-THR- ASN-ASN-ASN-LEU- CYF

			Metals

					_CD

			Waters ×51

* Residue conservation analysis

PDB id:

2mpa

Links

Name:

Immune system

Title:

Bactericidal antibody against neisseria meningitidis

Structure:

Mn12h2 igg2a-kappa, light chain. Chain: l. Fragment: fab fragment. Mn12h2 igg2a-kappa,heavy chain. Chain: h. Fragment: fab fragment. Conjugate of pora p1.16 peptide with fluorescein. Chain: p. Fragment: apex of extracellular loop 4 (vr2) of pora, residues 180 -

Source:

Mus musculus. Mouse, mouse. Organism_taxid: 10090. Strain: balb/c. Cell_line: mn12h2 murine-murine hybridoma. Cell: b-lymphocyte hybridoma. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Biol. unit:

Monomer (from PDB file)

Resolution:

2.60Å

R-factor:

0.202

R-free:

0.264

Authors:

J.M.H.Van Den Elsen,J.N.Herron,J.Kroon,P.Gros

Key ref:

J.M.van den Elsen et al. (1997). Bactericidal antibody recognition of a PorA epitope of Neisseria meningitidis: crystal structure of a Fab fragment in complex with a fluorescein-conjugated peptide. Proteins, 29, 113-125. PubMed id: 9294871

Date:

09-Jun-99

Release date:

23-Jun-99

PROCHECK

	Headers

	References

Protein chain

A2NHM3 (A2NHM3_MOUSE) - If kappa light chain (Fragment) from Mus musculus

Seq: Struc:					219 a.a. 219 a.a.*

Protein chain

Q569X1 (Q569X1_MOUSE) - Ighg protein from Mus musculus

Seq: Struc:					476 a.a. 224 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 76 residue positions (black crosses)

	Proteins 29:113-125 (1997)
PubMed id: 9294871

Bactericidal antibody recognition of a PorA epitope of Neisseria meningitidis: crystal structure of a Fab fragment in complex with a fluorescein-conjugated peptide.
J.M.van den Elsen, J.N.Herron, P.Hoogerhout, J.T.Poolman, E.Boel, T.Logtenberg, J.Wilting, D.J.Crommelin, J.Kroon, P.Gros.

ABSTRACT

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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

16314412

S.Staelens, M.A.Hadders, S.Vauterin, C.Platteau, M.De Maeyer, K.Vanhoorelbeke, E.G.Huizinga, and H.Deckmyn (2006).
Paratope determination of the antithrombotic antibody 82D6A3 based on the crystal structure of its complex with the von Willebrand factor A3-domain.

J Biol Chem, 281, 2225-2231.

PDB code:

2adf

12819059

E.Wedege, B.Kuipers, K.Bolstad, H.van Dijken, L.O.Frøholm, C.Vermont, D.A.Caugant, and G.van den Dobbelsteen (2003).
Antibody specificities and effect of meningococcal carriage in icelandic teenagers receiving the Norwegian serogroup B outer membrane vesicle vaccine.

Infect Immun, 71, 3775-3781.

11101301

A.P.Campbell, W.Y.Wong, R.T.Irvin, and B.D.Sykes (2000).
Interaction of a bacterially expressed peptide from the receptor binding domain of Pseudomonas aeruginosa pili strain PAK with a cross-reactive antibody: conformation of the bound peptide.

Biochemistry, 39, 14847-14864.

10722576

J.Wang, G.A.Jarvis, M.Achtman, E.Rosenqvist, T.E.Michaelsen, A.Aase, and J.M.Griffiss (2000).
Functional activities and immunoglobulin variable regions of human and murine monoclonal antibodies specific for the P1.7 PorA protein loop of Neisseria meningitidis.

Infect Immun, 68, 1871-1878.

9880525

J.van den Elsen, L.Vandeputte-Rutten, J.Kroon, and P.Gros (1999).
Bactericidal antibody recognition of meningococcal PorA by induced fit. Comparison of liganded and unliganded Fab structures.

J Biol Chem, 274, 1495-1501.

PDB code:

1mnu

9738009

S.Vasudevan, T.Tsuruo, and D.R.Rose (1998).
Mode of binding of anti-P-glycoprotein antibody MRK-16 to its antigen. A crystallographic and molecular modeling study.

J Biol Chem, 273, 25413-25419.

PDB code:

1bln

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.