A structural perspective on the interaction between lipopolysaccharide and Factor C, a receptor involved in recognition of Gram-negative bacteria
A structural perspective on the interaction between lipopolysaccharide and Factor C, a receptor involved in recognition of Gram-negative bacteria
复制标题
DOI：
10.1074/jbc.m609198200
复制
发表时间：
2007-02-09
影响因子：
4.8
通讯作者：
Kawabata, Shun-ichiro
中科院分区：
文献类型：
--
作者：
Koshiba, Takumi;Hashii, Tornoyuki;Kawabata, Shun-ichiro
对广泛保守的微生物成分（称为病原体相关分子模式）的识别是启动先天免疫反应的重要步骤。在鲎中，脂多糖 (LPS) 刺激血细胞会激活其先天免疫反应，而 C 因子（一种丝氨酸蛋白酶原）在这一过程中发挥着重要作用。在此，我们报道了 C 因子与血细胞表面的 LPS 结合并直接识别革兰氏阴性细菌。结构功能分析表明，LPS 结合位点存在于该分子的 N 端富含半胱氨酸（Cys-rich）区域，并且包含一个三肽序列，该序列由一个芳香族残基组成，两侧是两个碱性残基，这在其他哺乳动物 LPS 识别蛋白中是保守的。此外，我们还证明富含Cys的区域与革兰氏阴性细菌上的LPS特异性结合，并且三肽基序的突变消除了其与LPS和革兰氏阴性细菌的关联，强调了三肽在LPS相互作用中的重要性。尽管鲎对 LPS 的先天免疫反应与哺乳动物不同，但它似乎依赖于不同物种的 LPS 识别蛋白中保守的结构特征。
The recognition of broadly conserved microorganism components known as pathogen-associated molecular patterns is an essential step in initiating the innate immune response. In the horseshoe crab, stimulation of hemocytes with lipopolysaccharide (LPS) causes the activation of its innate immune response, and Factor C, a serine protease zymogen, plays an important role in this event. Here, we report that Factor C associates with LPS on the hemocyte surface and directly recognizes Gram-negative bacteria. Structure-function analyses reveal that the LPS binding site is present in the N-terminal cysteine-rich (Cys-rich) region of the molecule and that it contains a tripeptide sequence consisting of an aromatic residue flanked by two basic residues that is conserved in other mammalian LPS-recognizing proteins. Moreover, we have demonstrated that the Cys-rich region specifically binds to LPS on Gram-negative bacteria and that mutations in the tripeptide motif abrogate its association with both LPS and Gram-negative bacteria, underscoring the importance of the tripeptide in LPS interaction. Although the innate immune response to LPS in the horseshoe crab is distinct from that of mammals, it appears to rely on structural features that are conserved among LPS-recognizing proteins from diverse species.