Role of the hypervariable region in streptococcal M proteins: binding of a XXXX complement inhibitor.

@entity1 @entity14390 @entity465
Antigenic variation allows pathogenic microorganisms to evade the immune system of the infected host. The variable structure must play an important role in pathogenesis, but its function is in most cases unknown. Here, we identify a function for the surface-exposed hypervariable region of streptococcal M5 protein, a virulence factor that inhibits phagocytosis. The hypervariable region of M5 was found to bind the @entity1 complement inhibitor @entity14390 ), a 42-kDa plasma protein. Plasma absorption experiments with M5-expressing bacteria showed that the interaction with @entity14390 occurs also under physiologic conditions. Studies of another extensively characterized M protein, M6, indicated that this protein also has a binding site for @entity14390 in the hypervariable region. The complement-inhibitory function of @entity14390 was retained after binding to streptococci, suggesting that bound @entity14390 protects bacteria against @entity465 . All available data now indicate that @entity14390 , or another @entity1 complement inhibitor, binds to the hypervariable region of M proteins. These findings provide insights into the forces that drive antigenic variation and may explain why the hypervariable region of M protein is essential for phagocytosis resistance. Moreover, these data add to a growing body of evidence that @entity1 complement inhibitors are major targets for pathogenic microorganisms.
