MAPPING OF THE IMMUNOGLOBULIN LIGHT CHAIN-BINDING SITE OF PROTEIN-L

Protein L is a cell surface protein expressed by some strains of the a naerobic bacterial species Peptostreptococcus magnus. The molecule bin ds specifically and with high affinity to immunoglobulins (Ig) of a wi de range of animal species. The Ig-binding activity is mediated throug h five highly homologous domains, each 72 to 76 amino acid residues lo ng, which interact with framework regions in the variable domain of Ig light chains. The interaction does not interfere with the antigen bin ding capacity of the antibody The fold of the Ig light chain-binding d omains of Protein L is comprised of an alpha-helix packed against a fo ur stranded beta-sheet and is similar to the fold of the IgG heavy cha in-binding domains of streptococcal protein G, despite the fact that t he two proteins show no significant sequence homology. In the present work, heteronuclear NMR spectroscopy has been utilized to define the i nteraction between the N-terminal Ig-binding domain of Protein L and t he variable domain of a human Ig kappa light chain. The Ig-binding reg ion of the Protein L domain involves most of the residues in the secon d 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 c hain-binding surface of Protein L thus resembles the surface of Protei n G which binds to the C gamma 1 domain of IgG, hut 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 infe cted host.