Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.
Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.
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因子H （FH）是补体活化的丰富调节因子，保护宿主细胞免受补体的自我攻击。在这里，我们通过解决FH的前四个结构域的晶体结构与它的目标C3b复合物提供了对FH的调控活性的见解。FH与C3b的多个结构域相互作用，覆盖了很大的扩展表面积。结构表明，FH通过竞争和静电斥力破坏C3转化酶的稳定性，FH通过为蛋白酶因子I提供结合平台实现C3b的蛋白水解降解，同时稳定了C3b的整体结构域排列。结果为补体调控提供了通用模型，并为FH和C3b的疾病相关突变提供了结构解释。
Factor H (FH) is an abundant regulator of complement activation and protects host cells from self-attack by complement. Here we provide insights into the regulatory activity of FH by solving the crystal structure of the first four domains of FH in complex with its target C3b. FH interacts with multiple domains of C3b, covering a large, extended surface area. The structure indicated that FH destabilizes the C3 convertase by competition and electrostatic repulsion and that FH enables proteolytic degradation of C3b by providing a binding platform for the protease factor I, while stabilizing the overall domain arrangement of C3b. The results offer general models for complement regulation and provide structural explanations for disease-related mutations in both FH and C3b.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
11.4
作者：
Bouma, B;de Groot, PG;Gros, P
通讯作者：
Gros, P
DOI：
10.1107/s0907444902016657
发表时间：
2002-11-01
影响因子：
2.2
作者：
Adams, PD;Grosse-Kunstleve, RW;Terwilliger, TC
通讯作者：
Terwilliger, TC