Berggård K, Lindahl G, Dahlbäck B, Blom A M
Department of Medical Microbiology, Dermatology and Infection, Lund University, Lund, Sweden.
Eur J Immunol. 2001 Sep;31(9):2771-80. doi: 10.1002/1521-4141(200109)31:9<2771::aid-immu2771>3.0.co;2-0.
Human complement regulators are important targets for pathogenic microorganisms. In one such interaction, Bordetella pertussis binds human C4b-binding protein (C4BP), a high-molecular-weight plasma protein that acts as inhibitor of the classical pathway of complement activation. At least two different B. pertussis surface components, one of which is the virulence factor filamentous hemagglutinin (FHA), contribute to the binding. We used a set of C4BP mutants and monoclonal antibodies to characterize the region in C4BP that binds B. pertussis and analyzed the salt sensitivity of the interaction. These studies indicated that positively charged residues at the interface between complement control protein modules 1-2 in the C4BP alpha-chain are important for binding, and that the site in C4BP that binds B. pertussis is very similar, but not identical, to the C4b-binding site. Bacteria-bound C4BP retained its complement regulatory function and B. pertussis selectively bound C4BP in human plasma, indicating that binding occurs also in vivo. Together, these findings indicate that B. pertussis exploits a site in C4BP, resembling that used by the natural ligand C4b.
人类补体调节蛋白是致病微生物的重要靶点。在一种这样的相互作用中，百日咳博德特氏菌结合人C4b结合蛋白（C4BP），一种高分子量血浆蛋白，其作为补体激活经典途径的抑制剂。至少两种不同的百日咳博德特氏菌表面成分，其中之一是毒力因子丝状血凝素（FHA），参与这种结合。我们使用一组C4BP突变体和单克隆抗体来表征C4BP中与百日咳博德特氏菌结合的区域，并分析这种相互作用的盐敏感性。这些研究表明，C4BPα链中补体控制蛋白模块1-2之间界面处的带正电荷残基对于结合很重要，并且C4BP中与百日咳博德特氏菌结合的位点与C4b结合位点非常相似，但不完全相同。细菌结合的C4BP保留其补体调节功能，并且百日咳博德特氏菌在人血浆中选择性结合C4BP，表明这种结合也发生在体内。总之，这些发现表明百日咳博德特氏菌利用C4BP中的一个位点，类似于天然配体C4b所使用的位点。
