Alternaria alternata allergen Alt a 1: a unique β-barrel protein dimer found exclusively in fungi.
Alternaria alternata allergen Alt a 1: a unique β-barrel protein dimer found exclusively in fungi.
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DOI：
10.1016/j.jaci.2012.03.047
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发表时间：
2012-07
影响因子：
14.2
通讯作者：
Minor, Wladek
中科院分区：
文献类型：
--
作者：
Chruszcz, Maksymilian;Chapman, Martin D.;Osinski, Tomasz;Solberg, Robert;Demas, Matthew;Porebski, Przemyslaw J.;Majorek, Karolina A.;Pomes, Anna;Minor, Wladek
关键词：
链格孢属是与过敏性疾病相关的最常见的霉菌之一，并且80%的链格孢属敏感患者产生针对主要蛋白质过敏原Alt a 1的IgE抗体。Alt a 1的结构和功能尚不清楚。通过X射线晶体学方法获得Alt a 1的高分辨率结构，并研究Alt a 1与蛋白质数据库中报道的其他过敏原和蛋白质之间的结构关系。使用X射线晶体学来确定Alt a 1的结构，使用定制设计的一组结晶条件。通过Ta 6 Br 122+簇和单波长反常衍射的应用确定了初始Alt a 1模型。生物信息学分析用于比较Alt a1序列和结构与其他蛋白质。Alt a 1是一个独特的β-桶，包含11条β-链，并形成一个由单个二硫键连接的“蝴蝶样”二聚体，具有一个大的（1345 μ 2）二聚体界面。分子内二硫键在Alt a1同源物中是保守的。目前，Alt a1结构在蛋白质数据库中还没有等价物.生物信息学分析表明，这种结构只存在于真菌中。四个先前报道的推定的IgE结合肽已位于Alt a1结构上。Alt a 1具有独特的二聚体β-桶结构，似乎定义了一个新的蛋白质家族，其功能未知，仅在真菌中发现。Alt a 1的结构分析与IgE抗体结合表位的定位一致。Alt a 1的结构将为研究Alternaria过敏性变应性疾病的结构/功能机制和免疫学研究开辟新的途径。
Alternaria is one of the most common molds associated with allergic diseases and 80% of Alternaria-sensitive patients produce IgE antibodies to a major protein allergen, Alt a 1. The structure and function of Alt a 1 is unknown. To obtain a high resolution structure of Alt a 1 by X-ray crystallography and to investigate structural relationships between Alt a 1 and other allergens and proteins reported in the Protein Data Bank. X-ray crystallography was used to determine the structure of Alt a 1 using a custom-designed set of crystallization conditions. An initial Alt a 1 model was determined by the application of a Ta6Br122+ cluster and Single-wavelength Anomalous Diffraction. Bioinformatic analyses were used to compare the Alt a 1 sequence and structure with other proteins. Alt a 1 is a unique β-barrel comprising 11 β-strands and forms a ‘butterfly-like’ dimer linked by a single disulfide bond, with a large (1345Å2) dimer interface. Intramolecular disulfide bonds are conserved among Alt a 1 homologs. Currently, the Alt a 1 structure has no equivalent in the Protein Data Bank. Bioinformatics analyses suggest that the structure is found exclusively in fungi. Four previously reported putative IgE binding peptides have been located on the Alt a 1 structure. Alt a 1 has a unique, dimeric β-barrel structure that appears to define a new protein family with unknown function found exclusively in fungi. The location of IgE antibody binding epitopes is in agreement with the structural analysis of Alt a 1.The Alt a 1 structure will allow mechanistic structure/function studies and immunologic studies directed towards new forms of immunotherapy for Alternaria-sensitive allergic patients.
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影响因子：
3.6
作者：
DEARDS, MJ;MONTAGUE, AE
通讯作者：
MONTAGUE, AE
影响因子：
2.8
作者：
DeVouge, MW;Thaker, AJ;Vijay, HM
通讯作者：
Vijay, HM
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
影响因子：
14.2
作者：
Arbes, SJ;Sever, M;Zeldin, DC
通讯作者：
Zeldin, DC