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. 1995 Jan;63(1):149–153. doi: 10.1128/iai.63.1.149-153.1995

Location of the complement factor H binding site on streptococcal M6 protein.

V A Fischetti 1, R D Horstmann 1, V Pancholi 1
PMCID: PMC172971  PMID: 7806351

Abstract

The surface M protein of group A streptococci binds factor H, a regulatory protein of the alternative complement pathway, which may contribute to the antiphagocytic activity of the M molecules. To locate the factor H binding domain in the alpha-helical coiled-coil structure of the M molecule, the M protein was cleaved with pepsin at pH 5.8, which separates the molecule approximately in half. Western blot (immunoblot), amino acid sequence, and mass spectrometric analyses revealed that factor H bound to a 14.6-kDa C-terminal fragment of the M molecule. Competitive inhibition of factor H binding to the 14.6-kDa fragment with M protein peptides localized the binding site to amino acids 256 to 292. This segment is located within the surface-exposed region of the M6 protein, identified as the C-repeat region, whose sequence is conserved among heterologous M and M-like molecules. These studies also identified a second pepsin-susceptible site with the sequence ELAK located within the cell wall-associated region of the M molecule.

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Selected References

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