Ghosh Debajyoti, Gupta-Bhattacharya Swati
Department of Botany, Bose Institute, 93/1 A.P.C Road, Kolkata 700009, India.
Mol Immunol. 2008 Jan;45(2):456-62. doi: 10.1016/j.molimm.2007.05.025. Epub 2007 Jul 20.
Bet v 1 family is a large group of allergens present in pollen and plant-derived foods. They show similarity in sequence and 3D structure, properties often correlated to their cross-reactivity. protein T1 is a naturally occurring non-allergenic member of this group, which, in spite of having 35-85% sequence similarity, does not exhibit antibody-mediated cross-reactivity with other members of the Bet v 1 allergen family. This protein has been suggested to be a good model to study structural features critically needed for allergenicity and cross-reactivity.
Structural bioinformatic approach to analyze the properties of protein T1 in relation to allergenicity and cross-reactivity.
A 3D model of protein T1 was constructed by the homology modeling procedure and was compared to the structure of Bet v 1 with special reference to conservation, solvent accessibility and electrostatic properties of the residues across the antigenic surface.
The over-all fold of the homology model of T1 resembles that of the Bet v 1 group. The change in the solvent-accessible surface of the IgG (BV16)-binding residues has been quantified to be 75%. Comparing the allergenically potent dimer structure of Bet v 1 (predicted structure available in MSD of European Bioinformatics Institute), with the non-allergenic monomer, the BV16-binding surface and the p-loop seem to be of less importance for Bet v 1-mediated in vivo cross-linking of IgE. Instead, we think that other surface-exposed conserved patches are more significant. Absence of cross-reactivity between T1 and Bet v 1 comes from the lack of surface conservation leading to changes in the conformational as well as electrostatic properties. On the other hand, certain changes in the sequence, that might hinder dimerization of this protein, may result in the loss of allergenicity. Lastly, our structural docking experiment shows that protein T1 can bind two molecules of Brassinolide ligands like the other members of the Bet v 1 family.
Lack of dimerization and surface conservation might explain the reason why T1 is neither allergenic, nor cross-reactive to Bet v 1 group, although this protein can be a potential carrier for brassinosteroids.
Bet v 1家族是存在于花粉和植物源性食物中的一大类过敏原。它们在序列和三维结构上具有相似性，这些特性通常与其交叉反应性相关。蛋白质T1是该家族中一种天然存在的非过敏原成员，尽管其序列相似性为35%-85%，但它与Bet v 1过敏原家族的其他成员之间不存在抗体介导的交叉反应性。该蛋白质被认为是研究过敏原性和交叉反应性所需关键结构特征的良好模型。
采用结构生物信息学方法分析蛋白质T1与过敏原性和交叉反应性相关的特性。
通过同源建模程序构建蛋白质T1的三维模型，并与Bet v 1的结构进行比较，特别参考抗原表面残基的保守性、溶剂可及性和静电性质。
T1同源模型的整体折叠结构与Bet v 1家族相似。已量化IgG（BV16）结合残基的溶剂可及表面变化为75%。将Bet v 1的过敏原性二聚体结构（欧洲生物信息学研究所MSD中可获得的预测结构）与非过敏原单体进行比较，BV16结合表面和p环似乎对Bet v 1介导的体内IgE交联不太重要。相反，我们认为其他表面暴露的保守区域更重要。T1与Bet v 1之间缺乏交叉反应性是由于表面缺乏保守性，导致构象和静电性质发生变化。另一方面，序列中的某些变化可能会阻碍该蛋白质形成二聚体，从而可能导致过敏原性丧失。最后，我们的结构对接实验表明，蛋白质T1可以像Bet v 1家族的其他成员一样结合两分子油菜素内酯配体。
缺乏二聚化和表面保守性可能解释了T1既无过敏原性，也与Bet v 1家族无交叉反应性的原因，尽管该蛋白质可能是油菜素类固醇的潜在载体。
