Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complement
Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complement
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DOI：
10.1016/s0162-3109(00)80300-8
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发表时间：
2000-08-01
期刊：
影响因子：
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通讯作者：
Pangburn, MK
中科院分区：
文献类型：
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作者：
Pangburn, MK
H 因子负责识别宿主细胞和组织，并在补体旁路途径 (AP) 激活过程中介导微生物病原体的区分。其独特的 20 个 SCR 结构域以柔性链排列的结构允许多种功能位点在单分子组合化学的生物学示例中与补体蛋白和表面标记物相互作用。除了位于 N 端四个 SCR 结构域的补体调节位点外，另外两个位点结合补体蛋白 C3b，另外三个位点似乎识别充当宿主标记的各种聚阴离子。最近的研究表明，几个C3b和聚阴离子结合位点之间的协同作用影响H因子的生物学功能，并且每个位点对不同细胞的影响程度不同。一个或多个宿主标记识别位点的接合使得因子II能够控制AP的激活。由于缺乏类宿主标记，AP 会被激活，但许多常见病原体已经形成了 H 因子受体或不同程度真实性的宿主标记的模拟物，使它们能够逃避这种先天防御系统的检测。使用一种或多种这些规避技术的生物体包括淋病奈瑟氏菌、化脓性链球菌、小肠结肠炎耶尔森氏菌、克氏锥虫和 HIV 病毒。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Factor H is responsible for recognition of host cells and tissues and mediates discrimination among microbial pathogens during activation of the alternative pathway of complement (AP). Its unique structure of 20 SCR domains arranged in a flexible chain permits a variety of functional sites to interact with complement proteins and surface markers in a biological example of single-molecule combinatorial chemistry. In addition to the complement regulatory site located in the N-terminal four SCR domains, two other sites bind complement protein C3b and three sites appear to recognize a Variety of polyanions that serve as host markers. Recent studies indicate that cooperativity among several C3b- and polyanion-binding sites influences the biological functions of factor H and that the degree of influence of each site varies on different cells. The engagement of one or more of the host marker recognition sites enables factor Il to control activation of the AP. The absence of host-like markers allows AP activation, but many common pathogens have developed receptors for factor H or mimics of host markers of varying degrees of authenticity allowing them to escape detection by this innate defense system. Organisms using one or more of these evasive techniques include Neisseria gonorrhoeae, Streptococcus pyogenes, Yersinia enterocolitica, Trypanosoma cruzi, and the HIV virus. (C) 2000 Elsevier Science B.V. All rights reserved.