Sticholysins, two pore-forming toxins produced by the Caribbean Sea anemone Stichodactyla helianthus: Their interaction with membranes
Sticholysins, two pore-forming toxins produced by the Caribbean Sea anemone Stichodactyla helianthus: Their interaction with membranes
复制标题
DOI：
10.1016/j.toxicon.2009.02.022
复制
发表时间：
2009-12-15
期刊：
影响因子：
2.8
通讯作者：
Lanio, Maria E.
中科院分区：
文献类型：
--
作者：
Alvarez, Carlos;Mancheno, Jose M.;Lanio, Maria E.
溶血素I和II （StI/II）是由加勒比海海葵Stichodactyla helianthus产生的成孔毒素（pft），属于放光素家族，是海葵中唯一发现的一类真核pft。至于这个家族的其他成员，Sts是无半胱氨酸的蛋白质，分子量约为20kda，高等电点（>9.5），并且偏爱含有鞘磷脂的膜。通过x射线晶体学对StII的三维结构进行了解析，结果表明它是由一个疏水β -三明治核心组成的，该核心两侧分别有两个A；包含残基14-23和128-135的螺旋。各种实验结果表明，前30个n端残基，包括一个螺旋，直接参与孔的形成。这个区域包含一个两亲延伸，在所有的放射线机会蛋白中都很保守，这是分子中唯一可以改变构象而不扰乱一般蛋白质折叠的部分；事实上，与模型膜的结合只会使Sts的常规二级结构含量略有增加。Sts以可溶性形式产生，但它们很容易结合到不同的细胞和模型膜系统，如脂质单层、胶束和脂质囊泡。值得注意的是，结合和孔隙形成步骤都严重依赖于膜的物理化学性质。事实上，大量毒素在含有鞘磷脂的膜上以高亲和力不可逆结合，而在缺乏鞘磷脂的膜上结合相对较低且可逆。SM和胆固醇的共同存在在很大程度上促进了结合和孔的形成。少量有利于非层状组织的脂质也增加了孔隙形成的效率。在细胞和模型膜上形成的功能孔直径约为2.0 nm，可能是由四个单体的n端α螺旋相对于双层正常倾斜31度形成的。实验证据支持这样一种假设，即溶血素和另一种放线酶——equinatoxin II，在膜上形成一个环形孔，其中多肽链和磷脂的极性头基团都参与其中。2009爱思唯尔有限公司版权所有。
Sticholysins (Sts) I and II (StI/II) are pore-forming toxins (PFTs) produced by the Caribbean Sea anemone Stichodactyla helianthus belonging to the actinoporin family, a unique class of eukaryotic PFTs exclusively found in sea anemones. As for the rest of the members of this family, Sts are cysteine-less proteins, with molecular weights around 20 kDa, high isoelectric points (>9.5), and a preference for sphingomyelin-containing membranes. A three-dimensional structure of StII, solved by X-ray crystallography, showed that it is composed of a hydrophobic beta-sandwich core flanked on the opposite sides by two a; helices comprising residues 14-23 and 128-135. A variety of experimental results indicate that the first thirty N-terminal residues, which include one of the helices, are directly involved in pore formation. This region contains an amphipathic stretch, well conserved in all actinoporins, which is the only portion of the molecule that can change conformation without perturbing the general protein fold; in fact, binding to model membranes only produces a slight increase in the regular secondary structure content of Sts. Sts are produced in soluble form but they readily bind to different cell and model membrane systems such as lipidic monolayers, micelles, and lipid vesicles. Remarkably, both the binding and pore-formation steps are critically dependent on the physicochemical nature of the membrane. In fact, a large population of toxin irreversibly binds with high affinity in membranes containing sphingomyelin whereas binding in membranes lacking this sphingolipid is relatively low and reversible. The joint presence of SM and cholesterol largely promotes binding and pore formation. Minor amounts of lipids favoring a non-lamellar organization also augment the efficiency of pore formation. The functional pore formed in cellular and model membranes has a diameter of similar to 2.0 nm and is presumably formed by the N-terminal alpha helices of four monomers tilted 31 degrees in relation to the bilayer normal. Experimental evidence supports the hypothesis that sticholysins, as well as equinatoxin II, another actinoporin, form a toroidal pore in membranes in which the polypeptide chains as well as the polar head groups of phospholipids are involved. (C) 2009 Elsevier Ltd. All rights reserved.