Mapping of the immunoglobulin light chain-binding site of protein L.
Protein L is a cell surface protein expressed by some strains of the anaerobic bacterial species Peptostreptococcus magnus. The molecule binds specifically and with high affinity to immunoglobulins (Ig) of a wide range of animal species. The Ig-binding activity is mediated through five highly homologous domains, each 72 to 76 amino acid residues long, which interact with framework regions in the variable domain of Ig light chains. The interaction does not interfere with the antigen binding capacity of the antibody. The fold of the Ig light chain-binding domains of Protein L is comprised of an alpha-helix packed against a four stranded beta-sheet and is similar to the fold of the IgG heavy chain-binding domains of streptococcal protein G, despite the fact that the two proteins show no significant sequence homology. In the present work, heteronuclear NMR spectroscopy has been utilized to define the interaction between the N-terminal Ig-binding domain of Protein L and the variable domain of a human Ig kappa light chain. The Ig-binding region of the Protein L domain involves most of the residues in the second beta-strand, the C-terminal residues of the alpha-helix and the loop connecting the alpha-helix with the third beta-strand. The Ig light chain-binding surface of Protein L thus resembles the surface of Protein G which binds to the C gamma 1 domain of IgG, but is different from the portion of Protein G involved in the contact with the C gamma 2-C gamma 3 interface region. The data suggest that the global fold shared by the Ig-binding domains of Proteins L and G provide bacteria with a flexible template for the evolution of surface structures capable of interacting with different conserved parts of Ig molecules of the infected host.
Wikström
M
M
Department of Physical Chemistry 2, Lund University, Sweden.
Sjöbring
U
U
Drakenberg
T
T
Forsén
S
S
Björck
L
L
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010462:Peptostreptococcus / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D001426:Bacterial Proteins; C055047:Ig L-binding protein, Peptostreptococcus; C034284:IgG Fc-binding protein, Streptococcus; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains