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Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface

Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface
Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface
The multidomain bacterial surface protein L (PpL) is a virulence factor expressed by only 10% of Peptostreptococcus magnus strains, and its expression is correlated with bacterial vaginosis. The molecular basis for its ability to recognize 60% of mammalian immunoglobulin light chain variable regions (V-L) has been described recently by x-ray crystallography, which suggested the presence of two V-L binding sites on each protein L domain (Graille, M., Stura, E. A., Housden, N.G., Beekingham, J.A., Bottomley, S. P., Beale, D., Taussig, M.J., Sutton, B.J., Gore, M. G., and Charbonnier, J. (2001) Structure, 679-687). Here, we report the crystal structure at 2.1 Angstrom resolution of a protein L mutant complexed to an Fab' fragment with only 50% of the VL residues interacting with PpL site 1 conserved. Comparison of the site 1 interface from both structures shows how protein L is able to accommodate these sequence differences and therefore bind to a large repertoire of Ig. The x-ray structure and NMR results confirm the existence of two V-L binding sites on a single protein L domain. These sites exhibit a remarkable structural mimicry of growth factors binding to their receptors. This could explain the protein L superantigenic activity on human B lymphocytes.
human growth hormone, X-ray diffraction, peptosreptoococcus, crystal-structure, binding domain, straphylococcus-aureus, extracellular domain, FAB fragment, EPO receptor, human-IGG
0021-9258
47500-47506
Graille, Marc
e978d6b6-70e5-4643-86f0-840443063e41
Harrison, Steven
d192a37b-e61c-4688-8433-859507b98759
Crump, Matthew P.
ed31b5fd-23f6-434c-a38c-da3cb7b27402
Findlow, Stuart C.
0a7193ad-45cf-4613-a35e-3fd019a92ebe
Housden, Nicholas G.
d2ad0930-bb93-4e13-a967-4ecdc84a48e4
Muller, Bruno H.
14ef8b02-2a2c-46d1-8474-9146d4892116
Battail-Poirot, Nicole
701cad70-2d1d-4afb-8757-1c107bc9e39f
Sibai, Geneviève
45a7138f-47d7-4ace-bf6d-baf4f4986054
Sutton, Brian J.
3dfb5c91-444b-49ed-98e0-9aa19d28e2de
Taussig, Michael J.
45581366-5853-48f3-a9dc-0c99d7ffe3d3
Jolivet-Reynaud, Colette
f1c9d4ed-d176-4501-bba7-487ada93a9ea
Gore, Michael G.
7bd6db4b-c5a2-4206-8666-b92208ba7979
Stura, Enrico A.
72c4fa9d-e90e-473c-8524-244b490936cb
Graille, Marc
e978d6b6-70e5-4643-86f0-840443063e41
Harrison, Steven
d192a37b-e61c-4688-8433-859507b98759
Crump, Matthew P.
ed31b5fd-23f6-434c-a38c-da3cb7b27402
Findlow, Stuart C.
0a7193ad-45cf-4613-a35e-3fd019a92ebe
Housden, Nicholas G.
d2ad0930-bb93-4e13-a967-4ecdc84a48e4
Muller, Bruno H.
14ef8b02-2a2c-46d1-8474-9146d4892116
Battail-Poirot, Nicole
701cad70-2d1d-4afb-8757-1c107bc9e39f
Sibai, Geneviève
45a7138f-47d7-4ace-bf6d-baf4f4986054
Sutton, Brian J.
3dfb5c91-444b-49ed-98e0-9aa19d28e2de
Taussig, Michael J.
45581366-5853-48f3-a9dc-0c99d7ffe3d3
Jolivet-Reynaud, Colette
f1c9d4ed-d176-4501-bba7-487ada93a9ea
Gore, Michael G.
7bd6db4b-c5a2-4206-8666-b92208ba7979
Stura, Enrico A.
72c4fa9d-e90e-473c-8524-244b490936cb

Graille, Marc, Harrison, Steven, Crump, Matthew P., Findlow, Stuart C., Housden, Nicholas G., Muller, Bruno H., Battail-Poirot, Nicole, Sibai, Geneviève, Sutton, Brian J., Taussig, Michael J., Jolivet-Reynaud, Colette, Gore, Michael G. and Stura, Enrico A. (2002) Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface. The Journal of Biological Chemistry, 277 (49), 47500-47506. (doi:10.1074/jbc.M206105200).

Record type: Article

Abstract

The multidomain bacterial surface protein L (PpL) is a virulence factor expressed by only 10% of Peptostreptococcus magnus strains, and its expression is correlated with bacterial vaginosis. The molecular basis for its ability to recognize 60% of mammalian immunoglobulin light chain variable regions (V-L) has been described recently by x-ray crystallography, which suggested the presence of two V-L binding sites on each protein L domain (Graille, M., Stura, E. A., Housden, N.G., Beekingham, J.A., Bottomley, S. P., Beale, D., Taussig, M.J., Sutton, B.J., Gore, M. G., and Charbonnier, J. (2001) Structure, 679-687). Here, we report the crystal structure at 2.1 Angstrom resolution of a protein L mutant complexed to an Fab' fragment with only 50% of the VL residues interacting with PpL site 1 conserved. Comparison of the site 1 interface from both structures shows how protein L is able to accommodate these sequence differences and therefore bind to a large repertoire of Ig. The x-ray structure and NMR results confirm the existence of two V-L binding sites on a single protein L domain. These sites exhibit a remarkable structural mimicry of growth factors binding to their receptors. This could explain the protein L superantigenic activity on human B lymphocytes.

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Submitted date: 19 June 2002
Published date: 8 September 2002
Keywords: human growth hormone, X-ray diffraction, peptosreptoococcus, crystal-structure, binding domain, straphylococcus-aureus, extracellular domain, FAB fragment, EPO receptor, human-IGG

Identifiers

Local EPrints ID: 24026
URI: http://eprints.soton.ac.uk/id/eprint/24026
ISSN: 0021-9258
PURE UUID: ed12316c-cbcb-42a9-b8db-837fb51a9806

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Date deposited: 17 Mar 2006
Last modified: 15 Mar 2024 06:51

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Contributors

Author: Marc Graille
Author: Steven Harrison
Author: Matthew P. Crump
Author: Stuart C. Findlow
Author: Nicholas G. Housden
Author: Bruno H. Muller
Author: Nicole Battail-Poirot
Author: Geneviève Sibai
Author: Brian J. Sutton
Author: Michael J. Taussig
Author: Colette Jolivet-Reynaud
Author: Michael G. Gore
Author: Enrico A. Stura

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