Solution structure of the Big domain from Streptococcus pneumoniae reveals a novel Ca2+-binding module.

Streptococcus pneumoniae is a pathogen causing acute respiratory infection, otitis media and some other severe diseases in human. In this study, the solution structure of a bacterial immunoglobulin-like (Big) domain from a putative S. pneumoniae surface protein SP0498 was determined by NMR spectroscopy. SP0498 Big domain adopts an eight-β-strand barrel-like fold, which is different in some aspects from the two-sheet sandwich-like fold of the canonical Ig-like domains. Intriguingly, we identified that the SP0498 Big domain was a Ca(2+) binding domain. The structure of the Big domain is different from those of the well known Ca(2+) binding domains, therefore revealing a novel Ca(2+)-binding module. Furthermore, we identified the critical residues responsible for the binding to Ca(2+). We are the first to report the interactions between the Big domain and Ca(2+) in terms of structure, suggesting an important role of the Big domain in many essential calcium-dependent cellular processes such as pathogenesis.