Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7
IntroductionPet lipocalins are respiratory allergens with a central hydrophobic ligand-binding cavity called a calyx. Molecules carried in the calyx by allergens are suggested to influence allergenicity, but little is known about the native ligands.MethodsTo provide more information on prospective l...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Allergy |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/falgy.2023.1133412/full |
| _version_ | 1811158907010154496 |
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| author | Jungki Min Alexander C. Y. Foo Scott A. Gabel Lalith Perera Eugene F. DeRose Anna Pomés Lars C. Pedersen Geoffrey A. Mueller |
| author_facet | Jungki Min Alexander C. Y. Foo Scott A. Gabel Lalith Perera Eugene F. DeRose Anna Pomés Lars C. Pedersen Geoffrey A. Mueller |
| author_sort | Jungki Min |
| collection | DOAJ |
| description | IntroductionPet lipocalins are respiratory allergens with a central hydrophobic ligand-binding cavity called a calyx. Molecules carried in the calyx by allergens are suggested to influence allergenicity, but little is known about the native ligands.MethodsTo provide more information on prospective ligands, we report crystal structures, NMR, molecular dynamics, and florescence studies of a dog lipocalin allergen Can f 1 and its closely related (and cross-reactive) cat allergen Fel d 7.ResultsStructural comparisons with reported lipocalins revealed that Can f 1 and Fel d 7 calyxes are open and positively charged while other dog lipocalin allergens are closed and negatively charged. We screened fatty acids as surrogate ligands, and found that Can f 1 and Fel d 7 bind multiple ligands with preferences for palmitic acid (16:0) among saturated fatty acids and oleic acid (18:1 cis-9) among unsaturated ones. NMR analysis of methyl probes reveals that conformational changes occur upon binding of pinolenic acid inside the calyx. Molecular dynamics simulation shows that the carboxylic group of fatty acids shuttles between two positively charged amino acids inside the Can f 1 and Fel d 7 calyx. Consistent with simulations, the stoichiometry of oleic acid-binding is 2:1 (fatty acid: protein) for Can f 1 and Fel d 7.DiscussionThe results provide valuable insights into the determinants of selectivity and candidate ligands for pet lipocalin allergens Can f 1 and Fel d 7. |
| first_indexed | 2024-04-10T05:32:19Z |
| format | Article |
| id | doaj.art-57e29a23f0cd4d248580f8720e11c005 |
| institution | Directory Open Access Journal |
| issn | 2673-6101 |
| language | English |
| last_indexed | 2024-04-10T05:32:19Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Allergy |
| spelling | doaj.art-57e29a23f0cd4d248580f8720e11c0052023-03-07T06:17:06ZengFrontiers Media S.A.Frontiers in Allergy2673-61012023-03-01410.3389/falgy.2023.11334121133412Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7Jungki Min0Alexander C. Y. Foo1Scott A. Gabel2Lalith Perera3Eugene F. DeRose4Anna Pomés5Lars C. Pedersen6Geoffrey A. Mueller7Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesBasic Research, InBio, Charlottesville, VA, United StatesGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesIntroductionPet lipocalins are respiratory allergens with a central hydrophobic ligand-binding cavity called a calyx. Molecules carried in the calyx by allergens are suggested to influence allergenicity, but little is known about the native ligands.MethodsTo provide more information on prospective ligands, we report crystal structures, NMR, molecular dynamics, and florescence studies of a dog lipocalin allergen Can f 1 and its closely related (and cross-reactive) cat allergen Fel d 7.ResultsStructural comparisons with reported lipocalins revealed that Can f 1 and Fel d 7 calyxes are open and positively charged while other dog lipocalin allergens are closed and negatively charged. We screened fatty acids as surrogate ligands, and found that Can f 1 and Fel d 7 bind multiple ligands with preferences for palmitic acid (16:0) among saturated fatty acids and oleic acid (18:1 cis-9) among unsaturated ones. NMR analysis of methyl probes reveals that conformational changes occur upon binding of pinolenic acid inside the calyx. Molecular dynamics simulation shows that the carboxylic group of fatty acids shuttles between two positively charged amino acids inside the Can f 1 and Fel d 7 calyx. Consistent with simulations, the stoichiometry of oleic acid-binding is 2:1 (fatty acid: protein) for Can f 1 and Fel d 7.DiscussionThe results provide valuable insights into the determinants of selectivity and candidate ligands for pet lipocalin allergens Can f 1 and Fel d 7.https://www.frontiersin.org/articles/10.3389/falgy.2023.1133412/fullallergendogcatlipocalinstructure |
| spellingShingle | Jungki Min Alexander C. Y. Foo Scott A. Gabel Lalith Perera Eugene F. DeRose Anna Pomés Lars C. Pedersen Geoffrey A. Mueller Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7 Frontiers in Allergy allergen dog cat lipocalin structure |
| title | Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7 |
| title_full | Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7 |
| title_fullStr | Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7 |
| title_full_unstemmed | Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7 |
| title_short | Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7 |
| title_sort | structural and ligand binding analysis of the pet allergens can f 1 and fel d 7 |
| topic | allergen dog cat lipocalin structure |
| url | https://www.frontiersin.org/articles/10.3389/falgy.2023.1133412/full |
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