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Complex between Peptostreptococcusmagnus ProteinL and a human antibody reveals structural convergence in the interaction modes of fab binding proteins

Complex between Peptostreptococcusmagnus ProteinL and a human antibody reveals structural convergence in the interaction modes of fab binding proteins
Complex between Peptostreptococcusmagnus ProteinL and a human antibody reveals structural convergence in the interaction modes of fab binding proteins
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 (V-L) 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 Angstrom. The asymmetric unit contains two Fab molecules sandwiching a single PpL domain, which contacts similar V-L framework regions of two light chains via independent interfaces. The residues contacted on V-L are remote from the hypervariable loops. One PpL-V-K 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 V-L. 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.
immunoglobulin binding proteins (IBP), antibody complex, cell surface protein, X-ray structure
0969-2126
679-687
Graille, M.
112fabab-6adb-47d8-bd1e-b446371e5a68
Stura, E.A.
43c87eeb-ec69-41bc-8a00-bf8f6e354bb4
Housden, N.G.
5fc2b5f1-a7da-4f20-b794-d7d8ef597d5d
Bottomley, S.P.
9e5f98e5-d93d-40b1-89ea-db79b8990182
Beale, D.
0910b6d7-2863-41d5-981d-939693d3f86b
Taussig, M.J.
1ec696f6-d3bd-4a73-8e58-675162dc300d
Sutton, B.J.
8866e85f-472c-4644-b90e-08826b40c348
Gore, M.G.
7bd6db4b-c5a2-4206-8666-b92208ba7979
Charbonnier, J.-B.
6145c5c2-ca3c-45f9-b90e-b8244127c573
Graille, M.
112fabab-6adb-47d8-bd1e-b446371e5a68
Stura, E.A.
43c87eeb-ec69-41bc-8a00-bf8f6e354bb4
Housden, N.G.
5fc2b5f1-a7da-4f20-b794-d7d8ef597d5d
Bottomley, S.P.
9e5f98e5-d93d-40b1-89ea-db79b8990182
Beale, D.
0910b6d7-2863-41d5-981d-939693d3f86b
Taussig, M.J.
1ec696f6-d3bd-4a73-8e58-675162dc300d
Sutton, B.J.
8866e85f-472c-4644-b90e-08826b40c348
Gore, M.G.
7bd6db4b-c5a2-4206-8666-b92208ba7979
Charbonnier, J.-B.
6145c5c2-ca3c-45f9-b90e-b8244127c573

Graille, M., Stura, E.A., Housden, N.G., Bottomley, S.P., Beale, D., Taussig, M.J., Sutton, B.J., Gore, M.G. and Charbonnier, J.-B. (2001) Complex between Peptostreptococcusmagnus ProteinL and a human antibody reveals structural convergence in the interaction modes of fab binding proteins. Structure, 9 (8), 679-687. (doi:10.1016/S0969-2126(01)00630-X). (Submitted)

Record type: Article

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 (V-L) 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 Angstrom. The asymmetric unit contains two Fab molecules sandwiching a single PpL domain, which contacts similar V-L framework regions of two light chains via independent interfaces. The residues contacted on V-L are remote from the hypervariable loops. One PpL-V-K 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 V-L. 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.

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Submitted date: 22 March 2001
Keywords: immunoglobulin binding proteins (IBP), antibody complex, cell surface protein, X-ray structure

Identifiers

Local EPrints ID: 25148
URI: http://eprints.soton.ac.uk/id/eprint/25148
ISSN: 0969-2126
PURE UUID: 89bf6574-a914-4a1a-ab55-ea7f5a9f35f1

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Date deposited: 06 Apr 2006
Last modified: 15 Mar 2024 07:00

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Contributors

Author: M. Graille
Author: E.A. Stura
Author: N.G. Housden
Author: S.P. Bottomley
Author: D. Beale
Author: M.J. Taussig
Author: B.J. Sutton
Author: M.G. Gore
Author: J.-B. Charbonnier

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