专题:Nature报道
人类病原体脑膜炎奈瑟球菌是细菌性脑膜炎和败血病性休克的一个主要病因,它拥有一种表面蛋白,即“H-因子结合蛋白”(fHbp),后者与“宿主互补调控因子H”结合,从而干涉免疫反应。
现在,“人互补调控因子H”与fHbp之间所形成的复合物的结构已被确定。它显示,细菌蛋白通过模仿糖胺聚糖来结合H-因子,这种聚糖自然出现在宿主内皮细胞上,在那里它们与H-因子结合来防止血管树(vascular tree)的互补调控损伤。这项工作对于抵抗脑膜炎球菌疾病的疫苗及疗法的开发具有重要意义。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 458, 890-893 (16 April 2009) | doi:10.1038/nature07769
Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates
Muriel C. Schneider1,4,5, Beverly E. Prosser2,4, Joseph J. E. Caesar2, Elisabeth Kugelberg1, Su Li1, Qian Zhang1, Sadik Quoraishi2, Janet E. Lovett2, Janet E. Deane2, Robert B. Sim3, Pietro Roversi2, Steven Johnson2, Christoph M. Tang1 & Susan M. Lea2
1 Centre for Molecular Microbiology and Infection, Imperial College, London SW7 2AZ, UK
2 Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
3 MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
4 These authors contributed equally to this work.
5 Present address: Harvard Medical School, Boston, Massachusetts 02115, USA.
The complement system is an essential component of the innate and acquired immune system1, and consists of a series of proteolytic cascades that are initiated by the presence of microorganisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including complement factor H (fH; ref. 2), a 155 kDa protein composed of 20 domains (termed complement control protein repeats). Many pathogens have evolved the ability to avoid immune-killing by recruiting host complement regulators3 and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface4. Here we present the structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, fH. The structure also indicates the molecular basis of the host-specificity of the interaction between fH and the meningococcus, and informs attempts to develop novel therapeutics and vaccines.