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Location of the complement factor H binding site on streptococcal M6 protein
V A Fischetti1, R D Horstmann, V Pancholi
1Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, New York 10021.
Infection and Immunity
|January 1, 1995
Summary
Group A Streptococcus M protein binds complement factor H via its C-terminal region, specifically amino acids 256-292. This interaction helps the bacteria evade immune cell phagocytosis.
Area of Science:
- Microbiology
- Immunology
- Structural Biology
Background:
- Group A Streptococcus (GAS) surface M protein is crucial for bacterial survival.
- M protein interacts with host factor H, a complement regulator, potentially aiding immune evasion.
- Understanding the M protein-factor H interaction site is key to developing novel therapeutics.
Purpose of the Study:
- To map the specific binding domain of factor H on the GAS M protein.
- To investigate the structural basis of M protein's antiphagocytic activity.
Main Methods:
- Pepsin digestion of M protein to generate fragments.
- Western blotting and mass spectrometry to identify factor H binding fragments.
- Competitive inhibition assays using M protein peptides to pinpoint the binding site.
Main Results:
- Factor H binds to a 14.6-kDa C-terminal fragment of the M protein.
- The factor H binding site was localized to amino acids 256–292 within the C-repeat region.
- A second pepsin cleavage site (ELAK) was identified in the cell wall-associated region.
Conclusions:
- The C-repeat region (amino acids 256–292) of M protein is essential for factor H binding.
- This interaction likely contributes significantly to the antiphagocytic properties of GAS.
- Identifying this binding site offers a target for disrupting GAS virulence mechanisms.