Structures of lysenin reveal a shared evolutionary origin for pore-forming proteins and its mode of sphingomyelin recognition.
Structures of lysenin reveal a shared evolutionary origin for pore-forming proteins and its mode of sphingomyelin recognition.
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溶烯蛋白的结构揭示了孔形成蛋白的共同进化起源及其鞘磷脂识别模式。
DOI：
10.1016/j.str.2012.06.011
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发表时间：
2012-09-05
期刊：
影响因子：
--
通讯作者：
Gilbert RJ
中科院分区：
文献类型：
--
作者：
De Colibus L;Sonnen AF;Morris KJ;Siebert CA;Abrusci P;Plitzko J;Hodnik V;Leippe M;Volpi E;Anderluh G;Gilbert RJ
孔形成蛋白从溶液插入膜中以产生损伤，经历通常伴随寡聚化的结构重排。Lysenin是一种产自赤子绦虫的致孔毒素，它能特异性地与鞘磷脂（SM）相互作用，并通过攻击寄生虫的细胞膜形成孔而赋予其天然免疫力。SM在细胞膜中具有重要作用，而胞溶素是一种常用的SM标记试剂。胞溶素的结构表明它与来自不同真核生物和原核生物的其他成孔蛋白具有共同的祖先。与SM的复合物显示了其识别的蛋白质，其中磷酸胆碱头基和一个酰基尾特异性结合的模式。脂质相互作用的研究和测定，使用活的靶细胞确认的功能依赖的胞溶素对这种形式的SM识别。Lysenin结合SM的头基和尾;尾占据β折叠的边缘。脂质结合和活细胞研究证实了SM识别的活性依赖性Lysenin与来自不同王国的孔形成蛋白有关Lysenin与细菌和真菌中发现的孔形成蛋白有关。De Colibus等人描述了不同Apo构象的胞溶素的结构，并与脂质鞘磷脂结合。他们绘制了它的进化关系，并使用亲和力测定和活细胞成像验证了结构的见解。
Pore-forming proteins insert from solution into membranes to create lesions, undergoing a structural rearrangement often accompanied by oligomerization. Lysenin, a pore-forming toxin from the earthworm Eisenia fetida, specifically interacts with sphingomyelin (SM) and may confer innate immunity against parasites by attacking their membranes to form pores. SM has important roles in cell membranes and lysenin is a popular SM-labeling reagent. The structure of lysenin suggests common ancestry with other pore-forming proteins from a diverse set of eukaryotes and prokaryotes. The complex with SM shows the mode of its recognition by a protein in which both the phosphocholine headgroup and one acyl tail are specifically bound. Lipid interaction studies and assays using viable target cells confirm the functional reliance of lysenin on this form of SM recognition. ► We report the structure of lysenin, a sphingomyelin (SM)-binding pore-forming protein ► Lysenin binds SM's headgroup and tail; the tail occupies the edge of a β sheet ► Lipid binding and live cell studies confirm activity dependence on SM recognition ► Lysenin is related to pore-forming proteins from disparate kingdoms Lysenin is related to pore-forming proteins found in bacteria and fungi. De Colibus et al. describe structures of lysenin in different Apo conformations and bound to the lipid sphingomyelin. They map its evolutionary relationships and validate structural insights using affinity assays and live cell imaging.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
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通讯作者：
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
Cowtan, K
DOI：
10.1107/s0907444904016427
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
Bricogne, G
影响因子：
3
作者：
Crowther, RA;Henderson, R;Smith, JM
通讯作者：
Smith, JM