Crystallographically Mapped Ligand Binding Differs in High and Low IgE Binding Isoforms of Birch Pollen Allergen Bet v 1
Crystallographically Mapped Ligand Binding Differs in High and Low IgE Binding Isoforms of Birch Pollen Allergen Bet v 1
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DOI：
10.1016/j.jmb.2012.05.016
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发表时间：
2012-09-07
影响因子：
5.6
通讯作者：
Brandstetter, Hans
中科院分区：
文献类型：
--
作者：
Kofler, Stefan;Asam, Claudia;Brandstetter, Hans
家族10的致病相关蛋白与多种配体结合的能力被认为对其生理和病理功能起着关键作用。特别是，白桦树花粉中的典型过敏原Bet v 1被描述为高度混杂的配体受体。然而，详细的识别机制，包括区分自然产生的Bet v1变体结合性质的特异性因素，还没有被很好地了解。在这里，我们报告了Bet v1变体的晶体结构，它与一组配体组成的络合物，分辨率高达1.2埃。疏水口袋中的残基30不仅区分了高、低IgE结合的Bet v1亚型，而且还导致了模型配体脱氧胆酸盐结合方式的剧烈变化。Bet v1与多个配体的三元晶体结构络合物与荧光报告1-苯胺基-8-萘磺酸盐一起解释了1-苯胺基-8-萘磺酸盐置换分析获得的异常荧光结合曲线。这些结构揭示了关键的相互作用残基，如Tyr83，并使Bet v1中所谓的疏水口袋的结合特异性和混杂合理化。Bet v1的分子间相互作用揭示了一种意想不到的复杂性，这对于充分了解它在生理和过敏背景下的作用是必不可少的。(C)2012爱思唯尔有限公司。保留所有权利。
The ability of pathogenesis-related proteins of family 10 to bind a broad spectrum of ligands is considered to play a key role for their physiological and pathological functions. In particular, Bet v 1, an archetypical allergen from birch pollen, is described as a highly promiscuous ligand acceptor. However, the detailed recognition mechanisms, including specificity factors discriminating binding properties of naturally occurring Bet v 1 variants, are poorly understood.Here, we report crystal structures of Bet v 1 variants in complex with an array of ligands at a resolution of up to 1.2 angstrom. Residue 30 within the hydrophobic pocket not only discriminates in high and low IgE binding Bet v 1 isoforms but also induces a drastic change in the binding mode of the model ligand deoxycholate. Ternary crystal structure complexes of Bet v 1 with several ligands together with the fluorogenic reporter 1-anilino-8-naphthalene sulfonate explain anomalous fluorescence binding curves obtained from 1-anilino-8-naphthalene sulfonate displacement assays. The structures reveal key interaction residues such as Tyr83 and rationalize both the binding specificity and promiscuity of the so-called hydrophobic pocket in Bet v 1.The intermolecular interactions of Bet v 1 reveal an unexpected complexity that will be indispensable to fully understand its roles within the physiological and allergenic context. (C) 2012 Elsevier Ltd. All rights reserved.