Biomedical Informatics Center, PGIMER, Chandigarh 160012, India.
J Mol Model. 2010 Dec;16(12):1883-93. doi: 10.1007/s00894-010-0680-1. Epub 2010 Mar 16.
Rubber trees infected with a host-specific cassiicolin toxin often experience considerable leaf fall, which in turn results in loss of crop productivity. It was recently revealed that cassiicolin-specific single-chain variable fragments (scFv) can successfully reduce the toxic effects of cassiicolin. However, the detailed mechanism of antibody action remains poorly understood. The primary sequence of the newly sequenced cassiicolin-specific scFv was highly homologous to several members of single-chain antibodies in the 14B7 family. In this study, with the aid of homology modeling, the three-dimensional structure of cassiicolin-specific scFv was elucidated, and was found to exhibit a characteristic immunoglobulin fold that mainly consists of β sheets. Additionally, molecular docking between the modeled scFv antibody and the available three-dimensional crystal structure of cassiicolin toxin was also performed. The predicted structural complex and the change in accessible surface area between the toxin and the scFv antibody upon complexation reveal the potential role of certain complementarity determining region (CDR) amino acid residues in the formation of the complex. These computational results suggest that mutagenesis experiments that are aimed at validating the model and improving the binding affinity of cassiicolin-specific scFv antibodies for the toxin should be performed.
橡胶树感染了宿主特异性的卡西米尔毒素后,往往会经历相当严重的落叶,从而导致作物产量的损失。最近发现,卡西米尔特异性的单链可变片段 (scFv) 可以成功减轻卡西米尔毒素的毒性作用。然而,抗体作用的详细机制仍知之甚少。新测序的卡西米尔特异性 scFv 的一级序列与 14B7 家族的几种单链抗体高度同源。在这项研究中,借助同源建模,阐明了卡西米尔特异性 scFv 的三维结构,发现其呈现出一种特征性的免疫球蛋白折叠,主要由β片层组成。此外,还对模型化的 scFv 抗体与卡西米尔毒素现有三维晶体结构之间进行了分子对接。预测的结构复合物以及复合物形成过程中毒素和 scFv 抗体之间可及表面积的变化揭示了某些互补决定区 (CDR) 氨基酸残基在复合物形成中的潜在作用。这些计算结果表明,应该进行旨在验证模型和提高卡西米尔特异性 scFv 抗体对毒素结合亲和力的诱变实验。