Structure of the functional form of the mosquito larvicidal Cry4Aa toxin from Bacillus thuringiensis at a 2.8-Angstrom resolution
Structure of the functional form of the mosquito larvicidal Cry4Aa toxin from Bacillus thuringiensis at a 2.8-Angstrom resolution
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DOI：
10.1128/jb.188.9.3391-3401.2006
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发表时间：
2006-05-01
影响因子：
3.2
通讯作者：
Lescar, J
中科院分区：
文献类型：
--
作者：
Boonserm, P;Mo, M;Lescar, J
来自苏云金芽孢杆菌的Cry4Aa δ-内毒素对库蚊、按蚊和伊蚊的幼虫有毒，这些蚊子是重要的人类热带疾病的媒介。为了设计具有可用作生物农药的改进效力的修饰毒素，我们以2.8埃的分辨率确定了该毒素的功能形式的结构。与其他Cry δ-内毒素一样，活化的Cry4Aa毒素由三个球状结构域组成，一个负责孔形成的七-α-螺旋束（结构域I）和以下两个与碳水化合物结合蛋白具有结构相似性的其他结构域：β-棱柱（结构域II）和植物凝集素样β-夹心（结构域III）。我们还研究了位于Cry4Aa的推定受体结合结构域II表面的三个环中的氨基酸取代和缺失对毒性的影响。我们的研究结果表明，一个循环是一个重要的决定因素的毒性，大概是通过附件的Cry4Aa的蚊子细胞的表面。Cry4Aa结构的可用性应指导针对Cry内毒素的靶特异性和膜插入的分子基础的进一步研究。
The Cry4Aa delta-endotoxin from Bacillus thuringiensis is toxic to larvae of Culex, Anopheles, and Aedes mosquitoes, which are vectors of important human tropical diseases. With the objective of designing modified toxins with improved potency that could be used as biopesticides, we determined the structure of this toxin in its functional form at a resolution of 2.8 angstrom. Like other Cry delta-endotoxins, the activated Cry4Aa toxin consists of three globular domains, a seven-alpha-helix bundle responsible for pore formation (domain I) and the following two other domains having structural similarities with carbohydrate binding proteins: a beta-prism (domain II) and a plant lectin-like beta-sandwich (domain III). We also studied the effect on toxicity of amino acid substitutions and deletions in three loops located at the surface of the putative receptor binding domain II of Cry4Aa. Our results indicate that one loop is an important determinant of toxicity, presumably through attachment of Cry4Aa to the surface of mosquito cells. The availability of the Cry4Aa structure should guide further investigations aimed at the molecular basis of the target specificity and membrane insertion of Cry endotoxins.