Sharma Ruchi, Singh Ashok Kumar, Umashankar Vetrivel
Bioinformation. 2009 Aug 18;4(1):12-8. doi: 10.6026/97320630004012.
Vaccination is the most effective technique suggested now days for allergy treatment. Recombinant-based approaches are mostly focused on genetic modification of allergens to produce molecules with reduced allergenic activity and conserved antigenicity. The molecules developed for vaccination in allergy possess significantly reduced allergenicity in terms of IgE binding, and therefore will not lead to anaphylactic reactions upon injection. This approach is probably feasible with every peptide allergen with known amino acid sequence. In this study an in silico approach was used to investigate allergenic protein sequences. Motif analysis of these sequences reveals the allergenic epitopes in the amino acid sequences. Physicochemical analysis of protein sequences shows that the homolog allergens of Ory s1 are highly correlated with the aromaticity, GRAVY and cysteine content. Moreover, phylogenetic analysis of Ory s1 with other sequences reveals that Oryza sativa japonica and Zea mays are close homologs, whilst Lolium perenne and Dactylis glomerata are found to be remote homologs. The multiple sequence alignment reveals of Ory s1 with all its homologs in this study reveals the high conservation of residues in DPBB_1 domain (amino acid residue positions 86- 164) and was found distinctly in all the sequences. These findings support the proposal that allergenic epitopes encompass conserved residues. The consensus allergenic was found to be mainly composed of hydrophobic residues. The functional sites of allergenic proteins reported in this study shall be attenuated to develop hypoallergenic vaccine. The sequence comparison strategy adopted in this study would pave way effective evolutionary analysis of these allergens.
疫苗接种是目前建议用于过敏治疗的最有效技术。基于重组的方法主要集中在对过敏原进行基因改造,以产生具有降低的过敏原活性和保守抗原性的分子。为过敏症疫苗接种而开发的分子在IgE结合方面具有显著降低的过敏原性,因此注射时不会引发过敏反应。这种方法可能适用于每一种具有已知氨基酸序列的肽过敏原。在本研究中,采用了一种计算机模拟方法来研究过敏原蛋白序列。对这些序列的基序分析揭示了氨基酸序列中的过敏原表位。蛋白质序列的物理化学分析表明,Ory s1的同源过敏原与芳香性、亲水性氨基酸平均系数(GRAVY)和半胱氨酸含量高度相关。此外,对Ory s1与其他序列的系统发育分析表明,粳稻和玉米是近亲同源物,而黑麦草和鸭茅则是远亲同源物。本研究中对Ory s1与其所有同源物的多序列比对揭示了DPBB_1结构域(氨基酸残基位置86 - 164)中残基的高度保守性,并且在所有序列中都明显存在。这些发现支持了过敏原表位包含保守残基的提议。发现共有过敏原主要由疏水残基组成。本研究中报道的过敏原蛋白的功能位点应进行弱化处理,以开发低过敏原疫苗。本研究采用的序列比较策略将为这些过敏原的有效进化分析铺平道路。