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PDBsum entry 1hez
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protein ligands Protein-protein interface(s) links
Antibody PDB id
1hez

 

 

 

 

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Contents
Protein chains
214 a.a. *
207 a.a. *
61 a.a. *
Ligands
IMD ×2
Waters ×112
* Residue conservation analysis
PDB id:
1hez
Name: Antibody
Title: Structure of p. Magnus protein l bound to a human igm fab.
Structure: Kappa light chain of ig. Chain: a, c. Fragment: 1-214. Heavy chain of ig. Chain: b, d. Fragment: 501-724. Protein l. Chain: e. Fragment: 820-880
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: b-lymphocyte. Finegoldia magna. Organism_taxid: 1260. Strain: 3316. Plasmid: pkk223-3
Biol. unit: Pentamer (from PQS)
Resolution:
2.70Å     R-factor:   0.215     R-free:   0.278
Authors: M.Graille,E.A.Stura,N.G.Housden,S.P.Bottomley,M.J.Taussig,B.J.Sutton, M.G.Gore,J.B.Charbonnier
Key ref:
M.Graille et al. (2001). Complex between Peptostreptococcus magnus protein L and a human antibody reveals structural convergence in the interaction modes of Fab binding proteins. Structure, 9, 679-687. PubMed id: 11587642 DOI: 10.1016/S0969-2126(01)00630-X
Date:
27-Nov-00     Release date:   10-Aug-01    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01834  (IGKC_HUMAN) -  Immunoglobulin kappa constant from Homo sapiens
Seq:
Struc: 		107 a.a.
214 a.a.
Protein chains
Pfam   ArchSchema ?
P01871  (IGHM_HUMAN) -  Immunoglobulin heavy constant mu from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		474 a.a.
207 a.a.*
Protein chain
Pfam   ArchSchema ?
Q51918  (Q51918_FINMA) -  Protein L from Finegoldia magna
Seq:
Struc: 		 
Seq:
Struc: 		992 a.a.
61 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 

 
DOI no: 10.1016/S0969-2126(01)00630-X Structure 9:679-687 (2001)
PubMed id: 11587642  
 
 
Complex between Peptostreptococcus magnus protein L and a human antibody reveals structural convergence in the interaction modes of Fab binding proteins.
M.Graille, E.A.Stura, N.G.Housden, J.A.Beckingham, S.P.Bottomley, D.Beale, M.J.Taussig, B.J.Sutton, M.G.Gore, J.B.Charbonnier.
 
  ABSTRACT  
 
BACKGROUND: Peptostreptococcus magnus protein L (PpL) is a multidomain, bacterial surface protein whose presence correlates with virulence. It consists of up to five homologous immunoglobulin binding domains that interact with the variable (VL) regions of kappa light chains found on two thirds of mammalian antibodies. RESULTS: We refined the crystal structure of the complex between a human antibody Fab fragment (2A2) and a single PpL domain (61 residues) to 2.7 A. The asymmetric unit contains two Fab molecules sandwiching a single PpL domain, which contacts similar VL framework regions of two light chains via independent interfaces. The residues contacted on VL are remote from the hypervariable loops. One PpL-Vkappa interface agrees with previous biochemical data, while the second is novel. Site-directed mutagenesis and analytical-centrifugation studies suggest that the two PpL binding sites have markedly different affinities for VL. The PpL residues in both interactions are well conserved among different Peptostreptococcus magnus strains. The Fab contact positions identified in the complex explain the high specificity of PpL for antibodies with kappa rather than lambda chains. CONCLUSIONS: The PpL-Fab complex shows the first interaction of a bacterial virulence factor with a Fab light chain outside the conventional combining site. Structural comparison with two other bacterial proteins interacting with the Fab heavy chain shows that PpL, structurally homologous to streptococcal SpG domains, shares with the latter a similar binding mode. These two bacterial surface proteins interact with their respective immunoglobulin regions through a similar beta zipper interaction.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. PpL domain C* Complexed with Human IgM Fab 2A2(a) Ribbon representation of the 2 Fab:1 PpL domain complex present in the asymmetric unit. The PpL domain C* (red) is sandwiched between two Fabs (blue and green). Light colors represent the light chains, and dark colors represent the heavy chains. Magenta highlights the CDR loops, as defined by Chothia [17], and positions the Fab-PpL interfaces relative to the combining site. Pseudo 2-fold axis symmetry relates the two Fabs, but both interfaces are not symmetrical.(b) Stereoview of the 2F[o] - F[c] electron density map contoured at 1s at the first V[L]-PpL interface. The letter L precedes amino acids from the Fab light chain. Green dotted lines depict the three hydrogen bonds between Fab and PpL main-chain atoms. The three other hydrogen bonds are shown in magenta and involve at least one side-chain atom.(c) Ribbon representation of the V[L] region of Fab that interacts with the PpL domain. Ten residues common to the first and second interfaces are in yellow. Positions in pink are only involved in the first interface, and those in light green are implicated only in the second interface. All figures were generated with MOLMOL [42] or TURBO-FRODO [43]

 
  The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 679-687) copyright 2001.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21568864 E.V.Sidorin, and T.F.Solov'eva (2011).
IgG-Binding Proteins of Bacteria.
  Biochemistry (Mosc), 76, 295-308.  
19758995 D.A.MacKenzie, L.E.Tailford, A.M.Hemmings, and N.Juge (2009).
Crystal structure of a mucus-binding protein repeat reveals an unexpected functional immunoglobulin binding activity.
  J Biol Chem, 284, 32444-32453.
PDB code: 3i57
18700046 H.Yang, J.Cao, L.Q.Li, X.Zhou, Q.L.Chen, W.T.Liao, Z.M.Wen, S.H.Jiang, R.Xu, J.A.Jia, X.Pan, Z.T.Qi, and W.Pan (2008).
Evolutional selection of a combinatorial phage library displaying randomly-rearranged various single domains of immunoglobulin (Ig)-binding proteins (IBPs) with four kinds of Ig molecules.
  BMC Microbiol, 8, 137.  
18486949 N.R.Watts, G.Cardone, J.G.Vethanayagam, N.Cheng, C.Hultgren, S.J.Stahl, A.C.Steven, M.Sällberg, and P.T.Wingfield (2008).
Non-canonical binding of an antibody resembling a naïve B cell receptor immunoglobulin to hepatitis B virus capsids.
  J Mol Biol, 379, 1119-1129.  
18694300 S.H.Jiang, J.F.Wang, R.Xu, Y.J.Liu, X.N.Wang, J.Cao, P.Zhao, Y.J.Shen, T.Yang, H.Yang, J.A.Jia, Q.L.Chen, and W.Pan (2008).
Alternate arrangement of PpL B3 domain and SpA D domain creates synergistic double-site binding to VH3 and Vkappa regions of fab.
  DNA Cell Biol, 27, 423-431.  
17404047 M.Zouali (2007).
Exploitation of host signaling pathways by B cell superantigens--potential strategies for developing targeted therapies in systemic autoimmunity.
  Ann N Y Acad Sci, 1095, 342-354.  
16724100 G.J.Silverman, and C.S.Goodyear (2006).
Confounding B-cell defences: lessons from a staphylococcal superantigen.
  Nat Rev Immunol, 6, 465-475.  
15688433 A.C.Roque, M.A.Taipa, and C.R.Lowe (2005).
Synthesis and screening of a rationally designed combinatorial library of affinity ligands mimicking protein L from Peptostreptococcus magnus.
  J Mol Recognit, 18, 213-224.  
15863479 D.J.Brockwell, G.S.Beddard, E.Paci, D.K.West, P.D.Olmsted, D.A.Smith, and S.E.Radford (2005).
Mechanically unfolding the small, topologically simple protein L.
  Biophys J, 89, 506-519.  
15857176 E.Nilsson, and A.Larsson (2005).
Chicken anti-protein L for the detection of small amounts of protein L in the presence of IgG.
  Hybridoma (Larchmt), 24, 112-114.  
15787626 I.S.Duarte, R.d.e. .L.Zollner, and S.M.Bueno (2005).
Protein L-agarose for adsorption of autoantibodies: a potential tool for extracorporeal treatment.
  Artif Organs, 29, 313-323.  
15930633 V.Granata, N.G.Housden, S.Harrison, C.Jolivet-Reynaud, M.G.Gore, and E.A.Stura (2005).
Comparison of the crystallization and crystal packing of two Fab single-site mutant protein L complexes.
  Acta Crystallogr D Biol Crystallogr, 61, 750-754.
PDB code: 1ymh
15186398 D.Smith, R.D'Argy, M.Nilsson, U.Yrlid, J.de Jersey, L.Björck, and M.J.Wick (2004).
Whole-body autoradiography reveals that the Peptostreptococcus magnus immunoglobulin-binding domains of protein L preferentially target B lymphocytes in the spleen and lymph nodes in vivo.
  Cell Microbiol, 6, 609-623.  
  15057307 F.Ghiotto, F.Fais, A.Valetto, E.Albesiano, S.Hashimoto, M.Dono, H.Ikematsu, S.L.Allen, J.Kolitz, K.R.Rai, M.Nardini, A.Tramontano, M.Ferrarini, and N.Chiorazzi (2004).
Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia.
  J Clin Invest, 113, 1008-1016.  
15485827 J.C.Peter, G.Wallukat, J.Tugler, D.Maurice, J.C.Roegel, J.P.Briand, and J.Hoebeke (2004).
Modulation of the M2 muscarinic acetylcholine receptor activity with monoclonal anti-M2 receptor antibody fragments.
  J Biol Chem, 279, 55697-55706.  
15155659 M.Viau, N.S.Longo, P.E.Lipsky, L.Björck, and M.Zouali (2004).
Specific in vivo deletion of B-cell subpopulations expressing human immunoglobulins by the B-cell superantigen protein L.
  Infect Immun, 72, 3515-3523.  
14668335 N.G.Housden, S.Harrison, H.R.Housden, K.A.Thomas, J.A.Beckingham, S.E.Roberts, S.P.Bottomley, M.Graille, E.Stura, and M.G.Gore (2004).
Observation and characterization of the interaction between a single immunoglobulin binding domain of protein L and two equivalents of human kappa light chains.
  J Biol Chem, 279, 9370-9378.  
12221088 M.Graille, S.Harrison, M.P.Crump, S.C.Findlow, N.G.Housden, B.H.Muller, N.Battail-Poirot, G.Sibaï, B.J.Sutton, M.J.Taussig, C.Jolivet-Reynaud, M.G.Gore, and E.A.Stura (2002).
Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface.
  J Biol Chem, 277, 47500-47506.
PDB code: 1mhh
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.

 

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