Suppr超能文献

变应原的瞬时二聚体。

Transient dimers of allergens.

机构信息

Department of Chemistry, University of Eastern Finland, Joensuu, Finland.

出版信息

PLoS One. 2010 Feb 5;5(2):e9037. doi: 10.1371/journal.pone.0009037.

Abstract

BACKGROUND

Allergen-mediated cross-linking of IgE antibodies bound to the FcepsilonRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking.

METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release.

CONCLUSIONS/SIGNIFICANCE: The results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.

摘要

背景

过敏原介导的 IgE 抗体与肥大细胞表面的 FcepsilonRI 受体结合的交联是 I 型过敏的关键特征。如果过敏原是同源二聚体,其变应原性会增强,因为它只需要一种类型的抗体而不是两种来交联。

方法/主要发现:对 55 个过敏原晶体结构的分析表明,它们中有 80%以对称二聚体或多聚体的形式存在于晶体中。大多数是瞬态二聚体,在细胞中通过共定位形成高蛋白质浓度时形成。天然质谱分析表明,天然过敏原确实在溶液中形成瞬态二聚体,而它们的低变应原性变体几乎仅以单体形式存在。我们创建了一个单体 Bos d 5 过敏原,并表明它诱导组胺释放的能力降低。

结论/意义:结果表明二聚化将是过敏原非常常见和必要的特征。因此,过敏原的纯单体变体的制备可能为特异性免疫治疗开辟新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa94/2816702/dbeac85834eb/pone.0009037.g001.jpg

相似文献

1
Transient dimers of allergens.
PLoS One. 2010 Feb 5;5(2):e9037. doi: 10.1371/journal.pone.0009037.
3
Dimerization of lipocalin allergens.
Sci Rep. 2015 Sep 8;5:13841. doi: 10.1038/srep13841.
4
Structural aspects of dog allergies: the crystal structure of a dog dander allergen Can f 4.
Mol Immunol. 2014 Sep;61(1):7-15. doi: 10.1016/j.molimm.2014.04.003. Epub 2014 May 21.
5
Structure of the major carrot allergen Dau c 1.
Acta Crystallogr D Biol Crystallogr. 2009 Nov;65(Pt 11):1206-12. doi: 10.1107/S0907444909034854. Epub 2009 Oct 22.
7
Hypoallergenic mutants of the Timothy grass pollen allergen Phl p 5 generated by proline mutations.
Int Arch Allergy Immunol. 2012;159(2):130-42. doi: 10.1159/000336651. Epub 2012 May 30.
8
The non-specific lipid transfer protein, Ara h 9, is an important allergen in peanut.
Clin Exp Allergy. 2009 Sep;39(9):1427-37. doi: 10.1111/j.1365-2222.2009.03312.x. Epub 2009 Jul 16.
9
Structural and Functional Characterization of the Hazelnut Allergen Cor a 8.
J Agric Food Chem. 2015 Oct 21;63(41):9150-8. doi: 10.1021/acs.jafc.5b03534. Epub 2015 Oct 7.

引用本文的文献

1
Can Physicochemical Properties Alter the Potency of Aeroallergens? Part 2 - Impact of Physicochemical Properties.
Curr Allergy Asthma Rep. 2024 Nov;24(11):609-617. doi: 10.1007/s11882-024-01173-7. Epub 2024 Sep 20.
2
On the role of antibody affinity and avidity in the IgE-mediated allergic response.
Allergy. 2025 Jan;80(1):37-46. doi: 10.1111/all.16248. Epub 2024 Aug 27.
3
Impact of Enolase in Allergic Disease.
Curr Allergy Asthma Rep. 2024 Oct;24(10):571-579. doi: 10.1007/s11882-024-01170-w. Epub 2024 Aug 21.
5
Thermostable allergens in canned fish: Evaluating risks for fish allergy.
Allergy. 2023 Dec;78(12):3221-3234. doi: 10.1111/all.15864. Epub 2023 Aug 31.
6
Impact of oligomerization on the allergenicity of allergens.
Clin Mol Allergy. 2022 Apr 29;20(1):5. doi: 10.1186/s12948-022-00172-1.
7
Inhalant Mammal-Derived Lipocalin Allergens and the Innate Immunity.
Front Allergy. 2022 Jan 27;2:824736. doi: 10.3389/falgy.2021.824736. eCollection 2021.
8
Structural Aspects of the Allergen-Antibody Interaction.
Front Immunol. 2020 Sep 2;11:2067. doi: 10.3389/fimmu.2020.02067. eCollection 2020.

本文引用的文献

1
Antigen aggregation decides the fate of the allergic immune response.
J Immunol. 2010 Jan 15;184(2):725-35. doi: 10.4049/jimmunol.0902080. Epub 2009 Dec 7.
2
Structures of two major allergens, Bla g 4 and Per a 4, from cockroaches and their IgE binding epitopes.
J Biol Chem. 2009 Jan 30;284(5):3148-3157. doi: 10.1074/jbc.M807209200. Epub 2008 Dec 4.
3
Current and future methods for evaluating the allergenic potential of proteins: international workshop report 23-25 October 2007.
Food Chem Toxicol. 2008 Sep;46(9):3219-25. doi: 10.1016/j.fct.2008.06.078. Epub 2008 Jul 2.
4
Crystal structure of a dimerized cockroach allergen Bla g 2 complexed with a monoclonal antibody.
J Biol Chem. 2008 Aug 15;283(33):22806-14. doi: 10.1074/jbc.M800937200. Epub 2008 Jun 2.
6
Allergens are distributed into few protein families and possess a restricted number of biochemical functions.
J Allergy Clin Immunol. 2008 Apr;121(4):847-52.e7. doi: 10.1016/j.jaci.2008.01.025.
7
IgE in allergy and asthma today.
Nat Rev Immunol. 2008 Mar;8(3):205-17. doi: 10.1038/nri2273.
9
Allergological implication of the quaternary hexameric structure of the cockroach allergen Per a 3.
Clin Exp Allergy. 2008 Mar;38(3):539-48. doi: 10.1111/j.1365-2222.2007.02910.x. Epub 2007 Dec 12.
10
The origin of protein interactions and allostery in colocalization.
Nature. 2007 Dec 13;450(7172):983-90. doi: 10.1038/nature06524.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验