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

Manne, Kartik ; Chattopadhyay, Debasish ; Agarwal, Vaibhav LU ; Blom, Anna M. LU ; Khare, Baldeep ; Chakravarthy, Srinivas ; Chang, Chungyu ; Ton-That, Hung and Narayana, Sthanam V.L. (2020) In Acta crystallographica. Section D, Structural biology 76. p.759-770
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BibA, C4b-binding proteins, group B streptococcus, immunogenic bacterial adhesins, three-helix-bundle-motif repeats
in
Acta crystallographica. Section D, Structural biology
volume
76
pages
12 pages
publisher
John Wiley and Sons
external identifiers
  • scopus:85088908979
  • pmid:32744258
ISSN
2059-7983
DOI
10.1107/S2059798320008116
language
English
LU publication?
yes
id
6ae81574-7cce-45c2-8461-fc4950250ced
date added to LUP
2020-08-12 09:54:33
date last changed
2021-04-13 03:58:16
@article{6ae81574-7cce-45c2-8461-fc4950250ced,
  abstract     = {<p>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.</p>},
  author       = {Manne, Kartik and Chattopadhyay, Debasish and Agarwal, Vaibhav and Blom, Anna M. and Khare, Baldeep and Chakravarthy, Srinivas and Chang, Chungyu and Ton-That, Hung and Narayana, Sthanam V.L.},
  issn         = {2059-7983},
  language     = {eng},
  pages        = {759--770},
  publisher    = {John Wiley and Sons},
  series       = {Acta crystallographica. Section D, Structural biology},
  title        = {Novel structure of the N-terminal helical domain of BibA, a group B streptococcus immunogenic bacterial adhesin},
  url          = {http://dx.doi.org/10.1107/S2059798320008116},
  doi          = {10.1107/S2059798320008116},
  volume       = {76},
  year         = {2020},
}