Schein Catherine H, Ivanciuc Ovidiu, Braun Werner
Sealy Center for Structural Biology, Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0857, USA.
J Agric Food Chem. 2005 Nov 2;53(22):8752-9. doi: 10.1021/jf051148a.
Although many sequences and linear IgE epitopes of allergenic proteins have been identified and archived in databases, structural and physicochemical discriminators that define their specific properties are lacking. Current bioinformatics tools for predicting the potential allergenicity of a novel protein use methods that were not designed to compare peptides. Novel tools to determine the quantitative sequence and three-dimensional (3D) relationships between IgE epitopes of major allergens from peanut and other foods have been implemented in the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/). These peptide comparison tools are based on five-dimensional physicochemical property (PCP) vectors. Sequences from SDAP proteins similar in their physicochemical properties to known epitopes of Ara h 1 and Ara h 2 were identified by calculating property distance (PD) values. A 3D model of Ara h 1 was generated to visualize the 3D structure and surface exposure of the epitope regions and peptides with a low PD value to them. Many sequences similar to the known epitopes were identified in related nut allergens, and others were within the sequences of Ara h 1 and Ara h 2. Some of the sequences with low PD values correspond to other known epitopes. Regions with low PD values to one another in Ara h 1 had similar predicted structure, on opposite sides of the internal dimer axis. The PD scale detected epitope pairs that are similar in structure and/or reactivity with patient IgE. The high immunogenicity and IgE reactivity of peanut allergen proteins might be due to the proteins' arrays of similar antigenic regions on opposite sides of a single protein structure.
尽管许多变应原蛋白的序列和线性IgE表位已被鉴定并存档于数据库中，但仍缺乏定义其特定性质的结构和物理化学鉴别指标。目前用于预测新型蛋白质潜在变应原性的生物信息学工具所使用的方法并非设计用于比较肽段。在变应原蛋白结构数据库（SDAP；http://fermi.utmb.edu/SDAP/）中已实施了新型工具，用于确定花生和其他食物中主要变应原的IgE表位之间的定量序列和三维（3D）关系。这些肽段比较工具基于五维物理化学性质（PCP）向量。通过计算性质距离（PD）值，鉴定出SDAP蛋白中物理化学性质与Ara h 1和Ara h 2已知表位相似的序列。生成了Ara h 1的3D模型，以可视化表位区域的3D结构和表面暴露情况以及与它们具有低PD值的肽段。在相关坚果变应原中鉴定出许多与已知表位相似的序列，其他序列则存在于Ara h 1和Ara h 2的序列内。一些低PD值的序列对应于其他已知表位。在Ara h 1中彼此具有低PD值的区域在内部二聚体轴的相对侧具有相似的预测结构。PD标度检测到在结构和/或与患者IgE的反应性方面相似的表位对。花生变应原蛋白的高免疫原性和IgE反应性可能归因于单个蛋白质结构相对侧上相似抗原区域的排列。
