Crystal Structure of Leucotoxin S Component
Crystal Structure of Leucotoxin S Component
复制标题
白细胞毒素 S 组分的晶体结构
DOI：
--
复制
发表时间：
2004
影响因子：
4.8
通讯作者：
L. Mourey
中科院分区：
文献类型：
--
作者：
V. Guillet;P. Roblin;S. Werner;M. Coraiola;G. Menestrina;H. Monteil;G. Prévost;L. Mourey
葡萄球菌杀白细胞素和γ-溶血素（白细胞毒素）是形成溶解性跨膜孔的双组分毒素。它们的细胞毒性活性需要S类组分和F类组分的协同缔合，作为形成异源寡聚膜缔合复合物的水溶性单体产生。产生Panton-Valentine杀白细胞素的菌株在临床上与皮肤病变和社区获得性肺炎相关。在先前的研究中，我们确定了来自Panton-Valentine杀白细胞素的F单体的晶体结构。为了获得关于白细胞毒素的第二组分的信息，使用在不对称单元中含有八个分子的四聚体晶体形式，将来自Panton-Valentine杀白细胞素的S蛋白的X射线结构解析到2.0 A的分辨率。该结构展示了膜接触中所涉及的结构域的不同构象，并说明了成孔白细胞毒素的序列和三级结构变异性。在一个关键的表面残基（Thr-28）的诱变研究进一步支持这些微异质性的组装的二分白细胞毒素发挥的重要作用。
Staphylococcal leucocidins and γ-hemolysins (leucotoxins) are bi-component toxins that form lytic transmembrane pores. Their cytotoxic activities require the synergistic association of a class S component and a class F component, produced as water-soluble monomers that form hetero-oligomeric membrane-associated complexes. Strains that produce the Panton-Valentine leucocidin are clinically associated with cutaneous lesions and community-acquired pneumonia. In a previous study, we determined the crystal structure of the F monomer from the Panton-Valentine leucocidin. To derive information on the second component of the leucotoxins, the x-ray structure of the S protein from the Panton-Valentine leucocidin was solved to 2.0 Å resolution using a tetragonal crystal form that contains eight molecules in the asymmetric unit. The structure demonstrates the different conformation of the domain involved in membrane contacts and illustrates sequence and tertiary structure variabilities of the pore-forming leucotoxins. Mutagenesis studies at a key surface residue (Thr-28) further support the important role played by these microheterogeneities for the assembly of the bipartite leucotoxins.