Structural analysis of the Laetiporus sulphureus hemolytic pore-forming lectin in complex with sugars
Structural analysis of the Laetiporus sulphureus hemolytic pore-forming lectin in complex with sugars
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DOI：
10.1074/jbc.m413933200
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发表时间：
2005-04-29
影响因子：
4.8
通讯作者：
Hermoso, JA
中科院分区：
文献类型：
--
作者：
Mancheño, JM;Tateno, H;Hermoso, JA
LSL是由寄生蘑菇硫磺菌（Laetiporus sulphureus）产生的凝集素，其表现出溶血和血凝活性。在这里，我们报告的晶体结构的LSL细化到2.6埃的分辨率确定的单一同晶置换方法与异常散射（SIRAS）信号的铂衍生物。结构表明LSL是六聚体，这也被分析超离心所证实。单体蛋白（35 kDa）由两个不同的模块组成：N-末端凝集素模块和孔形成模块。凝集素模块具有β-三叶形支架，其具有与已知与半乳糖相关碳水化合物相互作用的毒素中存在的那些结构相似性，所述半乳糖相关碳水化合物例如来自肉毒梭菌、相思豆毒素和蓖麻毒素的祖毒素的血凝素组分（HA 1）。另一方面，C-末端孔形成模块（由结构域2和3组成）表现出与来自革兰氏阴性细菌嗜水气单胞菌的β-孔形成毒素气溶素的结构域3和4以及来自产气荚膜梭菌的ε-毒素的结构域2和3的三维结构相似性。这一发现揭示了气溶素样毒素家族中存在共同的结构元件，这些元件可能直接参与膜孔的形成。LSL与乳糖和N-乙酰乳糖胺的复合物的晶体结构揭示了每个亚基的两个dissacharide结合位点，并允许识别参与糖结合的关键残基。
LSL is a lectin produced by the parasitic mushroom Laetiporus sulphureus, which exhibits hemolytic and hemagglutinating activities. Here, we report the crystal structure of LSL refined to 2.6-angstrom resolution determined by the single isomorphous replacement method with the anomalous scatter (SIRAS) signal of a platinum derivative. The structure reveals that LSL is hexameric, which was also shown by analytical ultracentrifugation. The monomeric protein (35 kDa) consists of two distinct modules: an N-terminal lectin module and a pore-forming module. The lectin module has a beta-trefoil scaffold that bears structural similarities to those present in toxins known to interact with galactose-related carbohydrates such as the hemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum, abrin, and ricin. On the other hand, the C-terminal pore-forming module (composed of domains 2 and 3) exhibits three-dimensional structural resemblances with domains 3 and 4 of the beta-pore-forming toxin aerolysin from the Gram-negative bacterium Aeromonas hydrophila, and domains 2 and 3 from the epsilon-toxin from Clostridium perfringens. This finding reveals the existence of common structural elements within the aerolysin-like family of toxins that could be directly involved in membrane-pore formation. The crystal structures of the complexes of LSL with lactose and N-acetyllactosamine reveal two dissacharide-binding sites per subunit and permits the identification of critical residues involved in sugar binding.