Evidence for Plasticity and Structural Mimicry at the Immunoglobulin Light Chain-Protein L Interface

Graille, Marc; Harrison, S.; Crump, Matthew P.; Findlow, Stuart C.; Housden, Nicholas G.; Müller, Bruno; Battail-Poirot, Nicole; Sibai, G.; Sutton, Brian J.; Taussig, Michael J.; Jolivet-Reynaud, Colette; Gore, Michael G.; Stura, E.A.

doi:10.1074/jbc.m206105200

Cited by 38 publications

(32 citation statements)

References 40 publications

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“…These are a human 1-chain ( 1 T ) described here and the other a human Fab (2A2 (10)). Additionally the binding of mutated PpL 3316 domains to a murine 9 (Fab 19D9D6) has been studied (12). All of these confirm the presence of two binding sites per domain although the elimination of site 2 for the murine 9 (Fab 19D9D6) has been demonstrated for the mutant D55A (12).…”

Section: Determination Of the Rates Of Dissociation Of The Complexes-mentioning

confidence: 59%

“…Additionally the binding of mutated PpL 3316 domains to a murine 9 (Fab 19D9D6) has been studied (12). All of these confirm the presence of two binding sites per domain although the elimination of site 2 for the murine 9 (Fab 19D9D6) has been demonstrated for the mutant D55A (12). Binding at the second site is not easily detected due to the presence of the much higher affinity site 1.…”

Section: Determination Of the Rates Of Dissociation Of The Complexes-mentioning

confidence: 64%

“…The mutation D55A eliminates a salt bridge and dramatically weakens or eliminates binding (12), and conversely, the mutation A66W is predicted to cause a steric clash removing binding at site 2. This is born out by fluorimetry experiments reported here and therefore the A66W PpL 3316 is suitable for determining the affinity of site 1.…”

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confidence: 99%

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Observation and Characterization of the Interaction between a Single Immunoglobulin Binding Domain of Protein L and Two Equivalents of Human κ Light Chains

Housden

Harrison

Housden

et al. 2004

Journal of Biological Chemistry

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Protein L is a multidomain cell wall bound protein found in ϳ10% of the Peptostreptococcal isolates (1) and contains a series of repeated domains, some of which are able to bind to immunoglobulins without initiating an immune response. Expression of this protein has been correlated to the virulence of these opportunistic pathogenic bacteria (1) that are found in the gastrointestinal and urogenital tracts (2). Its presence has been found to cause cellular responses such as histamine release from basophils and mast cells (3) presumably by crosslinking IgE molecules bound to surface Ig receptors.1 H NMR spectroscopy of a single Ig-binding domain of protein L (isolated from strain 312, PpL 312 ) 1 revealed that PpL 312 is a rigid structure consisting of a ␤-sheet, formed by two pairs of antiparallel ␤-strands, lying on top of a single ␣-helical section (4), with a flexible N terminus (5). Further NMR studies (6) led to the proposal that the binding site of PpL 312 for -chain involves residues from the second ␤-strand and from the loop between the third ␤-strand and the ␣-helix and located the binding site for PpL 312 on the -chain to the second ␤-strand and the two ␤-strands located on the outer surface of the framework region of the V L domain (7).Parallel studies on the binding interaction of a single Igbinding domain of protein L from strain 3316 (PpL 3316 ) found that it forms a high affinity complex with -chains with a K d of 112 nM (8, 9). The x-ray crystallographic structure of this domain has been determined in complex with the human antibody fragment, Fab 2A2, and revealed that two Fab 2A2 fragments can in fact bind to sites on opposite faces of PpL 3316 (10). Site 1 of PpL 3316 is that characterized by Beckingham et al. (9) and equivalent to the site studied on PpL 312 using NMR by Wikström et al. (5). Site 2 of PpL 3316 , involving part of the helix and strands 3 and 4, was identified for the first time by the crystallographic study (10). This site has not yet been characterized although preliminary studies suggested that the affinity of site 2 is lower than that of site 1 (10).By use of a program of site directed mutagenesis we have been able to derive the relative binding affinities of sites 1 and 2 and propose a mechanism by which PpL 3316 binds light chains that is consistent with published data. The hydroxyl group of Tyr 53 is important for the formation of a high affinity complex at site 1. Previous enzyme-linked immunosorbent assay experiments (11) have shown that nitration of Tyr 53 or its mutation to Phe dramatically increases the K d of the -chainPpL 3316 interaction. Another important residue at site 1 is Leu 57 . No binding of the 1 -chain used in these studies can be detected at site 1 of the mutant Y53F/L57H by fluorimetry or isothermal titration calorimetry, and this mutant is thus ideal for measuring the affinity at site 2.Important residues for binding at site 2 are Asp 55 and Ala 66 . The mutation D55A eliminates a salt bridge and dramatically weakens or eliminates binding (12), and co...

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Section: Determination Of the Rates Of Dissociation Of The Complexes-mentioning

confidence: 59%

Section: Determination Of the Rates Of Dissociation Of The Complexes-mentioning

confidence: 64%

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Observation and Characterization of the Interaction between a Single Immunoglobulin Binding Domain of Protein L and Two Equivalents of Human κ Light Chains

Housden

Harrison

Housden

et al. 2004

Journal of Biological Chemistry

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“…Because of its flexibility, it responds equally well to changes in its crystal environment or complexation status. The side chain conformation of Arg L27 is different in the HCV core peptide complex, the uncomplexed FabЈ, and the complex with Peptostreptococcus magnus protein L mutant D55A (without a bound Ag) (26). Thus, this difference is not clearly attributable to peptide binding.…”

Section: Structure Of the 19d9d6 Fabј 13-40 Peptide Complexmentioning

confidence: 96%

“…The molecular replacement for FabЈ 19D9D6 has been described in detail previously (20,26). In brief, the model PDB-ID ϭ 1UCB (27) was used in the molecular replacement using AMoRe (28) in advance of the light and heavy chain sequencing.…”

Section: Structures Determination and Refinementmentioning

confidence: 99%

Crystal Structure of a Hydrophobic Immunodominant Antigenic Site on Hepatitis C Virus Core Protein Complexed to Monoclonal Antibody 19D9D6

Ménez

Bossus

Müller

et al. 2003

The Journal of Immunology

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The first crystal structure of a complex between a hepatitis C virus (HCV) core protein-derived peptide (residues 13–40) and the Ab fragment of a murine mAb (19D9D6) has been solved, allowing determination of the recognized epitope and elucidation of its conformation. This Ab, raised against the first 120 residues of the core protein, recognizes core particles and strongly competes with anticore human Abs, suggesting that it is highly representative of the human anti-HCV core response. Its epitope lies within the first 45 aa of the protein, the major antigenic segment of core recognized both by murine and human Abs. Surprisingly, the recognized epitope (29–37: QIVGGVYLL) has an unusual preponderance of hydrophobic residues, some of which are buried in a small hydrophobic core in the nuclear magnetic resonance structure of the peptide (2–45) in solution, suggesting that the Ab may induce a structural rearrangement upon recognition. The flexibility may reside entirely within the Ag, since the Fab′-peptide complex structure at 2.34 Å shows that the Ab binding site is hardly perturbed by complexation. Given that the recognized residues are unlikely to be solvent exposed, we are left with the interesting possibility that Ab-core interactions may take place in a nonaqueous environment.

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Affinity Chromatography: Historical and Prospective Overview

Rowe

Khoury

Lowe

2012

Biopharmaceutical Production Technology

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Evidence for Plasticity and Structural Mimicry at the Immunoglobulin Light Chain-Protein L Interface

Cited by 38 publications

References 40 publications

Observation and Characterization of the Interaction between a Single Immunoglobulin Binding Domain of Protein L and Two Equivalents of Human κ Light Chains

Observation and Characterization of the Interaction between a Single Immunoglobulin Binding Domain of Protein L and Two Equivalents of Human κ Light Chains

Crystal Structure of a Hydrophobic Immunodominant Antigenic Site on Hepatitis C Virus Core Protein Complexed to Monoclonal Antibody 19D9D6

Affinity Chromatography: Historical and Prospective Overview

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