Novel structure of the N‐terminal helical domain of BibA, a group B streptococcus immunogenic bacterial adhesin. Issue 8 (3rd August 2020)

• Record Type: Journal Article
• Authors: Manne, Kartik; Chattopadhyay, Debasish; Agarwal, Vaibhav; Blom, Anna M.; Khare, Baldeep; Chakravarthy, Srinivas; Chang, Chungyu; Ton-That, Hung; Narayana, Sthanam V. L.
• Is Part Of: Acta crystallographica. Volume 76:Issue 8(2020)
• Page Start: 759
• Page End: 770
• Publication Date: 2020-08-03
• Subjects: BibA -- group B streptococcus -- immunogenic bacterial adhesins -- three‐helix‐bundle‐motif repeats -- C4b‐binding proteins; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798320008116
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : The X‐ray crystallographic structure of an N‐terminal fragment of group B streptococcus BibA (BibA126–398 ) and a low‐resolution structure of the full‐length N‐terminal domain (BibA34–400 ) determined using small‐angle X‐ray scattering are described. The association of the N‐terminal domain of BibA was localized to the C4BP α‐chain. Abstract : 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 (BibA126–398 ) and a low‐resolution small‐angle X‐ray scattering (SAXS) structure of the full‐length N‐terminal domain (BibA34–400 ) are described. The BibA126–398 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 BibA34–400 delayed the degradation of the protein, and circular dichroism spectroscopy of BibA34–400 suggested a similar secondary‐structure composition to that observed in the crystallized BibA126–398 fragment. A model was generated for the 92 N‐terminal residues (BibA34–125 ) using structural similarity prediction programs, and a BibA34–400 model was generated by combining the coordinates of BibA34–126 and BibA126–398 . The X‐ray structure of BibA126–398 and the model of BibA34–400 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.