Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein
Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein
复制标题
斑马鱼气溶素样蛋白受体识别和孔形成的结构基础
DOI：
10.15252/embr.201540851
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发表时间：
2016-02-01
期刊：
影响因子：
7.7
通讯作者：
Zhou, Cong-Zhao
中科院分区：
文献类型：
--
作者：
Jia, Ning;Liu, Nan;Zhou, Cong-Zhao
从细菌到脊椎动物，已经鉴定出各种溶气素样孔形成蛋白。然而，真核生物成员的受体识别和/或孔形成的机制仍然不清楚。在这里，我们提出了来自Danio rerio的脊椎动物溶气素样蛋白Dln1的第一个晶体和电子显微镜结构，在孔形成之前和之后。Dln1二聚体的每个亚基包括一个棱柱凝集素模块和一个溶气素模块。凝集素模块与高甘露糖聚糖的特异性结合引发溶气素模块以一种pH依赖的方式发生剧烈的构象变化，最终导致膜结合的八聚体孔的形成。结构分析结合计算模拟和生化分析表明，孔的形成过程具有不同于先前表征的细菌成员的激活机制。此外，Dln1及其同系物在硬骨鱼和七鳃鳗中普遍存在，这可能是一种新的鱼类特异性防御分子。
Various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. However, the mechanism of receptor recognition and/or pore formation of the eukaryotic members remains unknown. Here, we present the first crystal and electron microscopy structures of a vertebrate aerolysin-like protein from Danio rerio, termed Dln1, before and after pore formation. Each subunit of Dln1 dimer comprises a -prism lectin module followed by an aerolysin module. Specific binding of the lectin module toward high-mannose glycans triggers drastic conformational changes of the aerolysin module in a pH-dependent manner, ultimately resulting in the formation of a membrane-bound octameric pore. Structural analyses combined with computational simulations and biochemical assays suggest a pore-forming process with an activation mechanism distinct from the previously characterized bacterial members. Moreover, Dln1 and its homologs are ubiquitously distributed in bony fishes and lamprey, suggesting a novel fish-specific defense molecule.