Human kininogens interact with M protein, a bacterial surface protein and virulence determinant

Streptococcus pyogenes, the most significant streptococcal species in clinical medicine, expresses surface proteins with affinity for several human plasma proteins. Here we report that kininogens, the precursors to the vasoactive kinins, bind to the surface of S. pyogenes. M protein, a surface molec...

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Bibliographic Details
Published in:	Biochemical journal Vol. 305 ( Pt 1); no. 1; pp. 173 - 180
Main Authors:	Ben Nasr, A B, Herwald, H, Müller-Esterl, W, Björck, L
Format:	Journal Article
Language:	English
Published:	England 01-01-1995
Subjects:	Amino Acid Sequence Antibodies - metabolism Antibodies - pharmacology Antigens, Bacterial Bacterial Outer Membrane Proteins Bacterial Proteins - metabolism Binding Sites Carrier Proteins Enzyme-Linked Immunosorbent Assay Fibrinogen - metabolism Humans Kininogens - metabolism Molecular Sequence Data Peptide Mapping Protein Binding Streptococcus pyogenes - metabolism Streptococcus pyogenes - pathogenicity Virulence
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Summary:	Streptococcus pyogenes, the most significant streptococcal species in clinical medicine, expresses surface proteins with affinity for several human plasma proteins. Here we report that kininogens, the precursors to the vasoactive kinins, bind to the surface of S. pyogenes. M protein, a surface molecule and a major virulence factor-in these bacteria, occurs in > 80 different serotypes. Among 49 strains of S. pyogenes, all of different M serotypes, 41 bound radiolabelled kininogens, whereas 6 M protein-negative mutant strains showed no affinity. M protein of most serotypes bind fibrinogen, and among the 55 strains tested, binding of kininogens was closely correlated to fibrinogen binding (r = 0.88, P < 0.0001). Western blotting, slot binding and enzyme immunoassay experiments demonstrated that M proteins isolated from S. pyogenes of three different M protein serotypes (M1, M6 and M46) bound kininogens. The affinity between kininogens and M1 protein was determined to be 5 x 10(7) M-1 and < or = 10(6) M-1 for high molecular weight (H-kininogen) and low molecular weight kininogen, respectively. The kininogen binding site was tentatively mapped to the N-terminal portion of M1 protein, and this site does not overlap the specific and separate binding sites for albumin, IgG and fibrinogen using monoclonal antibodies to, and synthetic peptides of, the kininogen sequence, the major M protein-binding site(s) was mapped to the C-terminal portion of the H-kininogen light chain. We anticipate that the kininogen-M protein interaction contributes to the host-parasite relationship in S. pyogenes infections.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0264-6021 1470-8728
DOI:	10.1042/bj3050173