A covalent S-F heterodimer of leucotoxin reveals molecular plasticity of β-barrel pore-forming toxins
A covalent S-F heterodimer of leucotoxin reveals molecular plasticity of β-barrel pore-forming toxins
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DOI：
10.1002/prot.21900
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发表时间：
2008-04-01
影响因子：
2.9
通讯作者：
Mourey, Lionel
中科院分区：
文献类型：
--
作者：
Roblin, Pierre;Guillet, Valerie;Mourey, Lionel
葡萄球菌白细胞毒素、杀白细胞素和γ-溶血素是双组分β-桶孔形成毒素（β-PFT）。它们的产生与几种临床疾病有关。由于S类组分和F类组分的协同作用，它们具有细胞毒性活性，S类组分和F类组分作为水溶性单体分泌并形成异源寡聚跨膜孔，导致易感细胞裂解。结构信息目前可用于单体S和F蛋白和由相关α-溶血素形成的同源七聚体。这些结构说明了β-PFT组装的机械框架中的起点和终点。只有有限的结构数据存在的中间阶段，包括异源寡聚复合物的白细胞毒素。我们研究了负责维持最终的二分分子结构的蛋白质-蛋白质相互作用，并在这里描述了γ-溶血素的位点特异性交联异源二聚体（HlgA T28 C-HlgB N156 C）的高分辨率晶体结构和低分辨率溶液结构，它们分别通过X射线晶体学和小角X射线散射解决。这些结构揭示了β-PFT的分子可塑性，这可能有助于从膜结合单体到异二聚体的转变。
Staphylococcal leucotoxins, leucocidins, and gamma-hemolysins are bicomponent beta-barrel pore-forming toxins (beta-PFTs). Their production is associated with several clinical diseases. They have cytotoxic activity due to the synergistic action of a class S component and a class F component, which are secreted as water-soluble monomers and form hetero-oligomeric transmembrane pores, causing the lysis of susceptible cells. Structural information is currently available for the monomeric S and F proteins and the homoheptamer formed by the related alpha-hemolysin. These structures illustrate the start and end points in the mechanistic framework of beta-PFT assembly. Only limited structural data exist for the intermediate stages, including hetero-oligomeric complexes of leucotoxins. We investigated the protein-protein interactions responsible for maintaining the final bipartite molecular architecture and describe here the high-resolution crystal structure and low-resolution solution structure Of a site-specific cross-linked heterodimer of gamma-hemolysin (HlgA T28C-HlgB N156C), which were solved by X-ray crystallography and small angle X-ray scattering, respectively. These structures reveal a molecular plasticity of beta-PFTs, which may facilitate the transition from membrane-bound monomers to heter-odimers.