气候变化领域集成服务门户(CCPortal): Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation

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DOI	10.1073/pnas.2016772118
	Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation
	Cruz A.R.; den Boer M.A.; Strasser J.; Zwarthoff S.A.; Beurskens F.J.; de Haas C.J.C.; Aerts P.C.; Wang G.; de Jong R.N.; Bagnoli F.; van Strijp J.A.G.; van Kessel K.P.M.; Schuurman J.; Preiner J.; Heck A.J.R.; Rooijakkers S.H.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	Immunoglobulin (Ig) G molecules are essential players in the human immune response against bacterial infections. An important effector of IgG-dependent immunity is the induction of complement activation, a reaction that triggers a variety of responses that help kill bacteria. Antibody-dependent complement activation is promoted by the organization of target-bound IgGs into hexamers that are held together via noncovalent Fc-Fc interactions. Here we show that staphylococcal protein A (SpA), an important virulence factor and vaccine candidate of Staphylococcus aureus, effectively blocks IgG hexamerization and subsequent complement activation. Using native mass spectrometry and high-speed atomic force microscopy, we demonstrate that SpA blocks IgG hexamerization through competitive binding to the Fc-Fc interaction interface on IgG monomers. In concordance, we show that SpA interferes with the formation of (IgG)6:C1q complexes and prevents downstream complement activation on the surface of S. aureus. Finally, we demonstrate that IgG3 antibodies against S. aureus can potently induce complement activation and opsonophagocytic killing even in the presence of SpA. Together, our findings identify SpA as an immune evasion protein that specifically blocks IgG hexamerization. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antibodies \| complement \| IgG hexamerization \| staphylococcal protein A \| Staphylococcus aureus
语种	英语
scopus关键词	bevifimod; complement component C1q; Fc receptor; immunoglobulin G; immunoglobulin G antibody; immunoglobulin G3; virulence factor; Article; atomic force microscopy; complement activation; complement inhibition; controlled study; downstream processing; hexamerization; human; mass spectrometry; nonhuman; priority journal; protein binding; Staphylococcus aureus
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180631
作者单位	Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, Netherlands; Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, 3584 CH, Netherlands; Nano Structuring and Bio-Analytics Group, TIMed Center, University of Applied Sciences Upper Austria, Linz, 4020, Austria; Genmab, Utrecht, 3508 AD, Netherlands; School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China; GlaxoSmithKline (GSK) Siena, Siena, 53100, Italy
推荐引用方式 GB/T 7714	Cruz A.R.,den Boer M.A.,Strasser J.,et al. Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation[J],2021,118(7).
APA	Cruz A.R..,den Boer M.A..,Strasser J..,Zwarthoff S.A..,Beurskens F.J..,...&Rooijakkers S.H.M..(2021).Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Cruz A.R.,et al."Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).