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Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4
Several dog allergens cause allergic reactions in humans worldwide. Seven distinct dog allergens, designated Canis familiaris allergen 1 to 7 (Can f 1–Can f 7), have been identified thus far. Can f 6 shows high sequence similarity and cross-reactivity with Fel d 4 and Equ c 1, major cat and horse al...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365566/ https://www.ncbi.nlm.nih.gov/pubmed/30728436 http://dx.doi.org/10.1038/s41598-018-38134-w |
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author | Yamamoto, Kenji Ishibashi, Osamu Sugiura, Keisuke Ubatani, Miki Sakaguchi, Masaya Nakatsuji, Masatoshi Shimamoto, Shigeru Noda, Masanori Uchiyama, Susumu Fukutomi, Yuma Nishimura, Shigenori Inui, Takashi |
author_facet | Yamamoto, Kenji Ishibashi, Osamu Sugiura, Keisuke Ubatani, Miki Sakaguchi, Masaya Nakatsuji, Masatoshi Shimamoto, Shigeru Noda, Masanori Uchiyama, Susumu Fukutomi, Yuma Nishimura, Shigenori Inui, Takashi |
author_sort | Yamamoto, Kenji |
collection | PubMed |
description | Several dog allergens cause allergic reactions in humans worldwide. Seven distinct dog allergens, designated Canis familiaris allergen 1 to 7 (Can f 1–Can f 7), have been identified thus far. Can f 6 shows high sequence similarity and cross-reactivity with Fel d 4 and Equ c 1, major cat and horse allergens, respectively. This study was conducted on the allergenic epitopes of Can f 6 based on its structural characterization. We demonstrated that sera from 18 out of 38 (47%) dog-sensitized patients reacted to recombinant Can f 6 protein (rCan f 6). We then determined the crystal structure of rCan f 6 by X-ray crystallography, which exhibited a conserved tertiary structural architecture found in lipocalin family proteins. Based on the tertiary structure and sequence similarities with Fel d 4 and Equ c 1, we predicted three IgE-recognizing sites that are possibly involved in cross-reactivity. Substituting three successive amino acids in these sites to triple alanine decreased IgE reactivity to the allergen. However, the degree of reduction in IgE reactivity largely depended on the site mutated and the serum used, suggesting that Can f 6 is a polyvalent allergen containing multiple epitopes and Can f 6-reactive sera contain varied amounts of IgE recognising individual Can f 6 epitopes including those predicted in this study. We also demonstrated that the predicted epitopes are partly involved in IgE cross-reactivity to Fel d 4. Interestingly, the effect of the mutation depended on whether the protein was structured or denatured, indicating that the bona fide tertiary structure of Can f 6 is essential in determining its IgE epitopes. |
format | Online Article Text |
id | pubmed-6365566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63655662019-02-08 Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4 Yamamoto, Kenji Ishibashi, Osamu Sugiura, Keisuke Ubatani, Miki Sakaguchi, Masaya Nakatsuji, Masatoshi Shimamoto, Shigeru Noda, Masanori Uchiyama, Susumu Fukutomi, Yuma Nishimura, Shigenori Inui, Takashi Sci Rep Article Several dog allergens cause allergic reactions in humans worldwide. Seven distinct dog allergens, designated Canis familiaris allergen 1 to 7 (Can f 1–Can f 7), have been identified thus far. Can f 6 shows high sequence similarity and cross-reactivity with Fel d 4 and Equ c 1, major cat and horse allergens, respectively. This study was conducted on the allergenic epitopes of Can f 6 based on its structural characterization. We demonstrated that sera from 18 out of 38 (47%) dog-sensitized patients reacted to recombinant Can f 6 protein (rCan f 6). We then determined the crystal structure of rCan f 6 by X-ray crystallography, which exhibited a conserved tertiary structural architecture found in lipocalin family proteins. Based on the tertiary structure and sequence similarities with Fel d 4 and Equ c 1, we predicted three IgE-recognizing sites that are possibly involved in cross-reactivity. Substituting three successive amino acids in these sites to triple alanine decreased IgE reactivity to the allergen. However, the degree of reduction in IgE reactivity largely depended on the site mutated and the serum used, suggesting that Can f 6 is a polyvalent allergen containing multiple epitopes and Can f 6-reactive sera contain varied amounts of IgE recognising individual Can f 6 epitopes including those predicted in this study. We also demonstrated that the predicted epitopes are partly involved in IgE cross-reactivity to Fel d 4. Interestingly, the effect of the mutation depended on whether the protein was structured or denatured, indicating that the bona fide tertiary structure of Can f 6 is essential in determining its IgE epitopes. Nature Publishing Group UK 2019-02-06 /pmc/articles/PMC6365566/ /pubmed/30728436 http://dx.doi.org/10.1038/s41598-018-38134-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yamamoto, Kenji Ishibashi, Osamu Sugiura, Keisuke Ubatani, Miki Sakaguchi, Masaya Nakatsuji, Masatoshi Shimamoto, Shigeru Noda, Masanori Uchiyama, Susumu Fukutomi, Yuma Nishimura, Shigenori Inui, Takashi Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4 |
title | Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4 |
title_full | Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4 |
title_fullStr | Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4 |
title_full_unstemmed | Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4 |
title_short | Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4 |
title_sort | crystal structure of the dog allergen can f 6 and structure-based implications of its cross-reactivity with the cat allergen fel d 4 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365566/ https://www.ncbi.nlm.nih.gov/pubmed/30728436 http://dx.doi.org/10.1038/s41598-018-38134-w |
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