The mechanism of leukocytolysis and hemolysis of the Staphylococcal leukocidin and gamma-hemolysin

葡萄球菌杀白细胞素和γ-溶血素的白细胞溶解和溶血机制

• 批准号: 09460042
• 负责人: KAMIO Yoshiyuki
• 金额: $ 8.58万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09460042/
• 关键词: Staphylococcus aureus; Staphylococcal leukocidin; Staphylococcal gamma-hemolysine; Tow-component toxin; Pore-forming toxin; X-ray crystallography; 膜孔; 結晶解析; ブドウ球菌; プロテインキナーゼA

It is well known that the proteins which show gross similarities in their biological function(s) have primary structures which are similar to each other. However, recently even proteins which show dissimilarity in primary structures have been reported to have identical biological functions and the three-dimensional structures. The Staphylococcal channel-forming toxins are taken as an example. Staphylococcus aureus secretes leukocidin and gamma-hemolysin gamma -HL) into a culture medium as water soluble monomers. Leukocidin and r -HL contain two separate and synergistic protein components, LukF and LukS, and LukF and Hlg2 (or H gamma H), respectively. LukF and LukS of leukocidin, and LukF and Hlg2 of gamma -HL assemble into a ring-shaped complexes, in which the molar ratios of LukF to LukS or Hlg2, respectively are both 1 : 1, within human polymorphonuclear leukocyte membranes and erythrocyte membranes. In each case a transmembrane pore results with a functional diameter of 2.1-2.5 nm ; … More this leads to lyse the respective target cell. The cell specificities of leukocidin and gamma -HL are determined by LukS and Hlg2, respectively. Despite the 72% overall identity between the LukS and Hlg2 aminoacid sequences, the respective cell specificities are strictly defined, Within the year suported by Grant-in-Aid for Scientific Research (B), we clarified the following evidences.[I] The staphylococcal Panton-Valentine leukocidin (PVL) genes, [lukS-PV-lukF-PV] exist on the genome of a temperate bacteriophage phiPVL isolated from mitomycin C-induced Staphylococcus aureus V8 (ATCC 49775) [Kaneko et al., 1997. Biosci. Biotechnol. Biochem. 61, 1960-l962]. In this study, the complete nucleotide sequence of the phiPVL genome was analyzed, and the att sites (attL, attR, and attB) required for site-specific integration of phiPVL into the host chromosome were also determined.[II] Identification of the minimum segment essential for the Hlg2-specific function of staphylococcal gamma Hemolysin : The 5-residue K^<23>RLA^<127> of Hlg2 is the minimum segment essential for the Hlg2-specificfunction of staphylococcal gamma-hemolysin.[III] Identification of the minimum segment in which threonine 246 residue is a phosphorylation site by protein kinase A for the LukS-specific function of staphylococcal leukocidin : The minimum segment responsible for the LukS specific funcion of leukocidin was identified. We conclude that the 5-residue segment I^<242>K^<243>R^<244>S^<245>T^<246> is pivotal segment of LukS responsible for the LukS-function of the staphylococcal leukocidin.[IV] The Phosphorylation of LukS by Protein Kinase A is Crucial for the LukS-Specific Function of the Staphylococcal Leukocidin on Human Polymorphonuclear Leukocytes[V] Crystal structure of staphylococcal LukF delineates conformational changes accompaning formation of a transmembrane channel. Less

据报道，据报道，蛋白质的生物学功能（s）habe主要结构中的蛋白质是蛋白质的，但据报道，即使是蛋白质中，蛋白质也具有相同的生物学功能，并且蛋白质的白色不相差。葡萄球菌形成的毒素是溶菌蛋白γ-HL的例子。白细胞素的luks，伽马-HL的LUKF和HLG2组装成一个环的丛，其中LUKF与Luks或HLG2的摩尔比分别为1：1，在人类多脑膜膜和红细胞膜中的摩尔比尽管LUKS和HLG2氨基酸HLG2 TIVE细胞的特异性在2.1-2.5 nm和伽马-HL的总体身份中，我们确定了72％的总体身份。 （PVL）从丝裂霉素C诱导的金黄色葡萄球菌V8中分离出的基因（ATCC 49775）[Kaneko等人，1997年。 （还确定了宿主染色体所需的attl，att和attb。或葡萄球菌伽马血解素的hlg2特异性功能：5-递归k^<27> rla^<27> rla^<127> hlg2的hlg2是hlg2的。对于HLG2特异性粉状γ-脱糖素的必要条件。其中苏氨酸246残留物是蛋白激酶A的磷酸化位点，用于葡萄球菌白细胞素的特异性功能244> s^<245> t^<246>是luks响应的关键段跨膜通道

项目成果

Jun Kaneko: "An N-terminal region of LukF of Staphylococcal leukocidin/γ-hemolysin crucial for the biologica activity of the toxin" Biosci.Biotechnol.Biochem.62(7). 1465-1467 (1998)

Jun Kaneko：“葡萄球菌杀白细胞素/γ-溶血素的 LukF 的 N 末端区域对于毒素的生物活性至关重要”Biosci.Biotechnol.Biochem.62(7) (1998)。

J.Kaneko, A.L.Mascarenas, M.N.Huda, T.Tomita, and Y.Kamio: "An N-terminal region of LukF of Staphylococcal leukocidin/gamma-hemolysin crucial for the biologica activity of the toxin" Biosci.Biotechnol.Biochem.62 (7). 1465-1467 (1998)

J.Kaneko、A.L.Mascarenas、M.N.Huda、T.Tomita 和 Y.Kamio：“葡萄球菌杀白细胞素/γ-溶血素的 LukF N 末端区域对于毒素的生物活性至关重要”Biosci.Biotechnol.Biochem.62

Jun Kaneko: "Sequential binding of Staphylococcal γ-hemolysin to human erythrocytes and complex formmation of the hemolysin on the cell surface." Biosci.Biotech.Biochem.61(5). 846-851 (1997)

Jun Kaneko：“葡萄球菌 γ-溶血素与人红细胞的顺序结合以及细胞表面溶血素的复合物形成。”Biosci.Biotech.Biochem.61(5) (1997)。

H.Nariya et al: "Identification of the minimum segment in which threonine^<246> residue is phosphorylated by protein kinase A for the LukS-specific function of staphylococcal leukocidin." FEBS Lett. 415. 96-100 (1997)

H.Nariya 等人：“鉴定了苏氨酸 ^ 246 残基被蛋白激酶 A 磷酸化的最小片段，以实现葡萄球菌杀白细胞素的 LukS 特异性功能。”

金子淳: "ロイコシジンとγヘモリジン遺伝子の起源と溶血機構に迫る" 化学と生物(解説). 36. 160-165 (1998)

Jun Kaneko：“了解杀白细胞素和 γ-溶血素基因的起源和溶血机制”《化学与生物学》（评论）36. 160-165 (1998)。