Structural and bioinformatic analysis of the kiwifruit allergen Act d 11, a member of the family of ripening-related proteins.
Structural and bioinformatic analysis of the kiwifruit allergen Act d 11, a member of the family of ripening-related proteins.
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DOI：
10.1016/j.molimm.2013.07.004
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发表时间：
2013-12
影响因子：
3.6
通讯作者：
Minor W
中科院分区：
文献类型：
--
作者：
Chruszcz M;Ciardiello MA;Osinski T;Majorek KA;Giangrieco I;Font J;Breiteneder H;Thalassinos K;Minor W
过敏原Act d 11，也称为kirola，是一种17 kDa的蛋白质，在成熟的绿色和黄色果肉猕猴桃中大量表达。10%的猕猴桃过敏者会产生对这种蛋白质特异的IgE。使用X射线晶体学，我们确定了Act d 11的第一个三维结构，该结构是从在E.大肠杆菌和天然来源（猕猴桃）。虽然Act d 11与桦树花粉过敏原Bet v 1和发病相关蛋白家族10（PR-10）的其他成员在免疫学上相关，但它与PR-10蛋白的序列相似性较低。根据序列，Act d 11似乎属于主要的乳胶/成熟相关（MLP/RRP）家族，但晶体结构分析显示Act d 11具有与Bet v 1和其他PR-10相关变应原非常相似的折叠，而不管低序列同一性。天然和重组蛋白的结构都包括一个未鉴定的配体，它相对较小（质谱实验约为250 Da），最有可能含有一个芳环。Act d 11中的配体结合腔也显著小于PR-10蛋白中的配体结合腔。配体的结合，我们不能明确地确定，结果在蛋白质的构象变化，可能有生理和免疫学的影响。有趣的是，对应于Bet v 1中Glu 45的残基（Glu 46）对于IgE与桦树花粉过敏原的结合是重要的，在Act d 11中是保守的，即使它在与Bet v 1具有显著更高序列同一性的其他过敏原中不是保守的。我们认为，所谓的富含甘氨酸的环（或P-环），这是保守的所有PR-10过敏原，可能是负责IgE之间的交叉反应性Betv 1和Act d 11。
The allergen Act d 11, also known as kirola, is a 17 kDa protein expressed in large amounts in ripe green and yellow-fleshed kiwifruit. Ten percent of all kiwifruit-allergic individuals produce IgE specific for the protein. Using X-ray crystallography, we determined the first three-dimensional structures of Act d 11, produced from both recombinant expression in E. coli and from the natural source (kiwifruit). While Act d 11 is immunologically correlated with the birch pollen allergen Bet v 1 and other members of the pathogenesis-related protein family 10 (PR-10), it has low sequence similarity to PR-10 proteins. By sequence Act d 11 appears instead to belong to the major latex/ripening-related (MLP/RRP) family, but analysis of the crystal structures shows that Act d 11 has a fold very similar to that of Bet v 1 and other PR-10 related allergens regardless of the low sequence identity. The structures of both the natural and recombinant protein include an unidentified ligand, which is relatively small (about 250 Da by mass spectroscopy experiments) and most likely contains an aromatic ring. The ligand-binding cavity in Act d 11 is also significantly smaller than those in PR-10 proteins. The binding of the ligand, which we were not able to unambiguously identify, results in conformational changes in the protein that may have physiological and immunological implications. Interestingly, residue corresponding to Glu45 in Bet v 1 (Glu46), which is important for IgE binding to the birch pollen allergen, is conserved in Act d 11, even though it is not in other allergens with significantly higher sequence identity to Bet v 1. We suggest that the so-called Gly-rich loop (or P-loop), which is conserved in all PR-10 allergens, may be responsible for IgE cross-reactivity between Bet v 1 and Act d 11.
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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
影响因子：
4
作者：
Berkner, Hanna;Neudecker, Philipp;Roesch, Paul
通讯作者：
Roesch, Paul
DOI：
10.1107/s0907444992007698
发表时间：
1993-01-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
COWTAN, KD;MAIN, P
通讯作者：
MAIN, P
影响因子：
5.4
作者：
Fernandes, Humberto;Bujacz, Anna;Jaskolski, Mariusz
通讯作者：
Jaskolski, Mariusz
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC