Structural and Dynamic Properties of Allergen and Non-Allergen Forms of Tropomyosin.
Structural and Dynamic Properties of Allergen and Non-Allergen Forms of Tropomyosin.
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DOI：
10.1016/j.str.2018.05.002
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发表时间：
2018-07-03
期刊：
影响因子：
--
通讯作者：
Nanda V
中科院分区：
文献类型：
--
作者：
James JK;Pike DH;Khan IJ;Nanda V
食物过敏原蛋白质的结构和生物物理特征在多大程度上将它们与我们饮食中的其他蛋白质区分开来？无脊椎动物原肌球蛋白（Tpm）作为一类被认为是“泛过敏原”，诱导对贝类的食物过敏和对尘螨的呼吸道过敏。已知脊椎动物Tpms不会引起过敏或交叉反应，尽管它们与无脊椎动物同源物具有高度的结构相似性和序列同一性。我们预期过敏原对胃肠道蛋白酶足够稳定，以在肠道中存活用于免疫致敏，并且蛋白水解稳定性将与热力学稳定性相关。虾Tpm的热变性表明，它比非过敏原脊椎动物Tpm更稳定。虾Tpm也更耐消化。分子动力学揭示了选择表位的局部动力学，以及虾和猪Tpm之间区分过敏原和非过敏原的灵活性的全局差异。变应原性的分子决定因素不仅取决于序列，而且取决于蛋白质结构和动力学的贡献。基于与现有过敏原的序列同源性预测新食物过敏原的预测模型在贝类过敏原原肌球蛋白上表现不佳，该蛋白与非过敏性脊椎动物形式具有高度同一性。相反，通过生物物理性质和结构动力学将过敏原与非过敏原区分开。
To what extent do structural and biophysical features of food allergen proteins distinguish them from other proteins in our diet? Invertebrate tropomyosins (Tpm) as a class are considered ‘pan-allergens’, inducing food allergy to shellfish and respiratory allergy to dust mites. Vertebrate Tpms are not known to elicit allergy or cross-reactivity, despite their high structural similarity and sequence identity to invertebrate homologs. We expect allergens are sufficiently stable against gastro-intestinal proteases to survive for immune sensitization in the intestines, and that proteolytic stability will correlate with thermodynamic stability. Thermal denaturation of shrimp Tpm shows that it is more stable than non-allergen vertebrate Tpm. Shrimp Tpm is also more resistant to digestion. Molecular dynamics uncover local dynamics that select epitopes, and global differences in flexibility between shrimp and pig Tpm that discriminate allergens from non-allergens. Molecular determinants of allergenicity depend not only on sequence but on contributions of protein structure and dynamics. Predictive models that anticipate new food allergens based on sequence homology to existing allergens, do not perform well on the shellfish allergen tropomyosin, which shares high identity with non-allergenic vertebrate forms. Instead, allergens are discriminated from non-allergens by biophysical properties and structural dynamics.
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影响因子：
2.8
作者：
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DOI：
10.1073/pnas.1101221108
发表时间：
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影响因子：
11.1
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通讯作者：
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