Crystal structure of the octameric pore of staphylococcal γ-hemolysin reveals the β-barrel pore formation mechanism by two components
Crystal structure of the octameric pore of staphylococcal γ-hemolysin reveals the β-barrel pore formation mechanism by two components
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DOI：
10.1073/pnas.1110402108
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发表时间：
2011-10
期刊：
影响因子：
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通讯作者：
K. Yamashita;Y. Kawai;Yoshikazu Tanaka;N. Hirano;J. Kaneko;N. Tomita;M. Ohta;Y. Kamio;M. Yao;I. Tanaka
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文献类型：
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作者：
K. Yamashita;Y. Kawai;Yoshikazu Tanaka;N. Hirano;J. Kaneko;N. Tomita;M. Ohta;Y. Kamio;M. Yao;I. Tanaka
葡萄球菌γ-溶血素是由LukF和Hlg 2组成的双组分成孔毒素。这些蛋白质表达为水溶性单体，然后在靶细胞上组装成寡聚孔形式。在这里，我们报告的八聚体孔形式的γ-溶血素的晶体结构在2.5 μ m分辨率，这是第一个高分辨率结构的β-桶跨膜蛋白组成的两个蛋白质的日期报告。八聚体组装体由LukF和Hlg 2的四个分子以圆形图案交替定位组成，这解释了过去二十年来积累的生化数据。结构，结合单体形式，展示了两种不同分子参与孔形成的精细分子机制，其中使用连接β2和β3的环的原异构体间静电相互作用（循环A：LukF的Asp 43-Lys 48和Hlg 2的Lys 37-Lys 43）作为通过N-末端β-链解旋进行组装的结构决定因素发挥关键作用在一个实施方案中，跨膜茎结构域与相邻原聚体的氨基锁（氨基锁）结合，释放在单体（前茎）中折叠成β折叠的跨膜茎结构域，并与相邻原聚体相互作用。
Staphylococcal γ-hemolysin is a bicomponent pore-forming toxin composed of LukF and Hlg2. These proteins are expressed as water-soluble monomers and then assemble into the oligomeric pore form on the target cell. Here, we report the crystal structure of the octameric pore form of γ-hemolysin at 2.5 Å resolution, which is the first high-resolution structure of a β-barrel transmembrane protein composed of two proteins reported to date. The octameric assembly consists of four molecules of LukF and Hlg2 located alternately in a circular pattern, which explains the biochemical data accumulated over the past two decades. The structure, in combination with the monomeric forms, demonstrates the elaborate molecular machinery involved in pore formation by two different molecules, in which interprotomer electrostatic interactions using loops connecting β2 and β3 (loop A: Asp43-Lys48 of LukF and Lys37-Lys43 of Hlg2) play pivotal roles as the structural determinants for assembly through unwinding of the N-terminal β-strands (amino-latch) of the adjacent protomer, releasing the transmembrane stem domain folded into a β-sheet in the monomer (prestem), and interaction with the adjacent protomer.