Staphylococcal Complement Evasion Protein Sbi Stabilises C3d Dimers by Inducing an N-Terminal Helix Swap

is an opportunistic pathogen that is able to thwart an effective host immune response by producing a range of immune evasion molecules, including binder of IgG (Sbi) which interacts directly with the central complement component C3, its fragments and associated regulators. Recently we reported the f...

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Bibliographic Details
Published in:Frontiers in immunology 2022-05, Vol.13, p.892234-892234
Main Authors: Dunphy, Rhys W, Wahid, Ayla A, Back, Catherine R, Martin, Rebecca L, Watts, Andrew G, Dodson, Charlotte A, Crennell, Susan J, van den Elsen, Jean M H
Format: Article
Language:English
Subjects:
3D domain swapping
Animals
Bacterial Proteins
C3d
Carrier Proteins - metabolism
complement
Disulfides - metabolism
Immunology
Rats
Staphylococcus - metabolism
Staphylococcus aureus
structural biology
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Summary:is an opportunistic pathogen that is able to thwart an effective host immune response by producing a range of immune evasion molecules, including 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 C3d dimer and highlighted its potential role in modulating B-cell activation. Here we present an X-ray crystal structure of a disulfide-linked human C3d 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.892234