Novel structure of the N‐terminal helical domain of BibA, a group B streptococcus immunogenic bacterial adhesin

BibA, a group B streptococcus (GBS) surface protein, has been shown to protect the pathogen from phagocytic killing by sequestering a complement inhibitor: C4b‐binding protein (C4BP). Here, the X‐ray crystallographic structure of a GBS BibA fragment (BibA 126–398 ) and a low‐resolution small‐angle X‐ray scattering (SAXS) structure of the full‐length N‐terminal domain (BibA 34–400 ) are described. The BibA 126–398 fragment crystal structure displayed a novel and predominantly helical structure. The tertiary arrangement of helices forms four antiparallel three‐helix‐bundle‐motif repeats, with one long helix from a bundle extending into the next. Multiple mutations on recombinant BibA 34–400 delayed the degradation of the protein, and circular dichroism spectroscopy of BibA 34–400 suggested a similar secondary‐structure composition to that observed in the crystallized BibA 126–398 fragment. A model was generated for the 92 N‐terminal residues (BibA 34–125 ) using structural similarity prediction programs, and a BibA 34–400 model was generated by combining the coordinates of BibA 34–126 and BibA 126–398 . The X‐ray structure of BibA 126–398 and the model of BibA 34–400 fitted well into the calculated SAXS envelope. One possible binding site for the BibA N‐terminal domain was localized to the N‐terminal CCP (complement‐control protein) domains of the C4BP α‐chain, as indicated by the decreased binding of BibA to a ΔCCP1 C4BP α‐chain mutant. In summary, it is suggested that the GBS surface protein BibA, which consists of three antiparallel α‐helical‐bundle motifs, is unique and belongs to a new class of Gram‐positive surface adhesins.