Staphylococcal complement evasion protein Sbi stabilises C3d dimers by inducing an N-terminal helix swap

Rhys Dunphy, Ayla Wahid, Catherine Back, Beccie Martin, Andrew Watts, Charlotte Dodson, Susan Crennell, Jean Van Den Elsen

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Staphylococcus aureus is an opportunistic pathogen that is able to thwart an effective host immune response by producing a range of immune evasion molecules, including S. aureus binder of IgG (Sbi) which interacts directly with the central complement component C3, its fragments and associated regulators. Recently we reported the first structure of a disulfide-linked human C3d17C dimer and highlighted its potential role in modulating B-cell activation. Here we present an X-ray crystal structure of a disulfide-linked human C3d17C dimer, which undergoes a structurally stabilising N-terminal 3D domain swap when in complex with Sbi. These structural studies, in combination with circular dichroism and fluorescence spectroscopic analyses, reveal the mechanism underpinning this unique helix swap event and could explain the origins of a previously discovered N-terminally truncated C3dg dimer isolated from rat serum. Overall, our study unveils a novel staphylococcal complement evasion mechanism which enables the pathogen to harness the ability of dimeric C3d to modulate B-cell activation.
Original languageEnglish
Article number892234
JournalFrontiers in Immunology
Early online date25 May 2022
Publication statusPublished - 25 May 2022

Bibliographical note

Funding Information:
This research was supported by the Biotechnology and Biological Sciences Research Council Follow On Fund BB/N022165/1. AAW was sponsored by a PhD studentship granted by Raoul and Catherine Hughes and the University of Bath Alumni Fund. RD was supported by a Medical Research Council GW4 Doctoral Training Partnership (MR/N0137941/1).


  • 3D domain swapping
  • C3d
  • Staphylococcus aureus
  • complement
  • structural biology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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