Structural and Interaction Insight in Streptococcal beta C Proteins

Abstract

Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. The study of GBS protein is important for understanding its pathogenesis and epidemiology of infection. To date, several GBS surface proteins with the ability to induce protective antibodies in animals have been reported, including beta C proteins. The beta C protein is a GBS surface protein being investigated as a potential vaccine candidate. Here, we constructed truncated beta C proteins in order to study the function of this protein. Factor H (fH) is involved in the process of complement activation and is a complement control protein. Its principal function is to regulate the alternative pathway of the complement system, playing a role in ensuring the complement system is directed towards pathogens rather than host cells. While it was previously reported that GBS binds to fH, how this occurs at the molecular level has remained unclear. We used truncated beta C proteins to map the interaction between fH and beta C to a defined region within the beta C molecule. In addition, we have determined a 2.36 Å resolution crystal structure of this portion of beta C, which reveals a variation upon the alpha helical bundle fold common in Gram‐positive innate immune evasion proteins. These findings enhance our knowledge of a major cell wall‐anchored surface protein of GBS and promote our understanding of its role in the pathogenesis of streptococcal disease.