Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17621-6. doi: 10.1073/pnas.1003750107. Epub 2010 Sep 27.
The complement system is a major target of immune evasion by Staphylococcus aureus. Although many evasion proteins have been described, little is known about their molecular mechanisms of action. Here we demonstrate that the extracellular fibrinogen-binding protein (Efb) from S. aureus acts as an allosteric inhibitor by inducing conformational changes in complement fragment C3b that propagate across several domains and influence functional regions far distant from the Efb binding site. Most notably, the inhibitor impaired the interaction of C3b with complement factor B and, consequently, formation of the active C3 convertase. As this enzyme complex is critical for both activation and amplification of the complement response, its allosteric inhibition likely represents a fundamental contribution to the overall immune evasion strategy of S. aureus.
补体系统是金黄色葡萄球菌免疫逃逸的主要目标。尽管已经描述了许多逃逸蛋白，但它们的作用分子机制知之甚少。在这里，我们证明金黄色葡萄球菌的细胞外纤维蛋白结合蛋白 (Efb) 作为变构抑制剂发挥作用，诱导补体片段 C3b 发生构象变化，这种变化在多个结构域中传播，并影响远离 Efb 结合位点的功能区域。值得注意的是，该抑制剂削弱了 C3b 与补体因子 B 的相互作用，进而影响了活性 C3 转化酶的形成。由于该酶复合物对于补体反应的激活和放大都至关重要，因此其变构抑制可能是金黄色葡萄球菌整体免疫逃逸策略的一个基本贡献。
