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sciadv.abf5325.pdf | 1.63 MB | Adobe PDF | 見る/開く |
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dc.contributor.author | Maeda, Shintaro | en |
dc.contributor.author | Shiimura, Yuki | en |
dc.contributor.author | Asada, Hidetsugu | en |
dc.contributor.author | Hirata, Kunio | en |
dc.contributor.author | Luo, Fangjia | en |
dc.contributor.author | Nango, Eriko | en |
dc.contributor.author | Tanaka, Nobuo | en |
dc.contributor.author | Toyomoto, Masayasu | en |
dc.contributor.author | Inoue, Asuka | en |
dc.contributor.author | Aoki, Junken | en |
dc.contributor.author | Iwata, So | en |
dc.contributor.author | Hagiwara, Masatoshi | en |
dc.contributor.alternative | 前田, 信太郎 | ja |
dc.contributor.alternative | 椎村, 祐樹 | ja |
dc.contributor.alternative | 浅田, 秀基 | ja |
dc.contributor.alternative | 平田, 邦生 | ja |
dc.contributor.alternative | 南後, 恵理子 | ja |
dc.contributor.alternative | 田中, 信生 | ja |
dc.contributor.alternative | 豊本, 雅靖 | ja |
dc.contributor.alternative | 井上, 飛鳥 | ja |
dc.contributor.alternative | 青木, 淳賢 | ja |
dc.contributor.alternative | 岩田, 想 | ja |
dc.contributor.alternative | 萩原, 正敏 | ja |
dc.date.accessioned | 2021-06-15T11:11:25Z | - |
dc.date.available | 2021-06-15T11:11:25Z | - |
dc.date.issued | 2021-06 | - |
dc.identifier.uri | http://hdl.handle.net/2433/263316 | - |
dc.description | 脂質受容体の新たな活性化機構を解明 --脂質がまっすぐ伸びて活性化--. 京都大学プレスリリース. 2021-06-10. | ja |
dc.description.abstract | Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution. S1P exhibits an unbent conformation in the long tunnel, which penetrates through the receptor obliquely. Compared with the inactive S1PR1 structure, four residues surrounding the alkyl tail of S1P (the “quartet core”) exhibit orchestrating rotamer changes that accommodate the moiety, thereby inducing an active conformation. In addition, we reveal that the quartet core determines G protein selectivity of S1PR3. These results offer insight into the structural basis of activation and biased signaling in G protein–coupled receptors and will help the design of biased ligands for optimized therapeutics. | en |
dc.language.iso | eng | - |
dc.publisher | American Association for the Advancement of Science (AAAS) | en |
dc.rights | Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. | en |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | - |
dc.title | Endogenous agonist–bound S1PR3 structure reveals determinants of G protein–subtype bias | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Science Advances | en |
dc.identifier.volume | 7 | - |
dc.identifier.issue | 24 | - |
dc.relation.doi | 10.1126/sciadv.abf5325 | - |
dc.textversion | publisher | - |
dc.identifier.artnum | eabf5325 | - |
dc.address | Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University; Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University | en |
dc.address | Department of Cell Biology, Graduate School of Medicine, Kyoto University; Institute of Life Science, Kurume University | en |
dc.address | Department of Cell Biology, Graduate School of Medicine, Kyoto University | en |
dc.address | RIKEN SPring-8 Center | en |
dc.address | Department of Cell Biology, Graduate School of Medicine, Kyoto University; RIKEN SPring-8 Center | en |
dc.address | Department of Cell Biology, Graduate School of Medicine, Kyoto University; RIKEN SPring-8 Center; Institute of Multidisciplinary Research for Advanced Materials, Tohoku University | en |
dc.address | Medical Research Support Center, Graduate School of Medicine, Kyoto University | en |
dc.address | Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University; Department of Drug Discovery for Lung Diseases, Graduate School of Medicine, Kyoto University | en |
dc.address | Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University | en |
dc.address | Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University | en |
dc.address | Department of Cell Biology, Graduate School of Medicine, Kyoto University; RIKEN SPring-8 Center | en |
dc.address | Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University; Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University; Medical Research Support Center, Graduate School of Medicine, Kyoto University; Department of Drug Discovery for Lung Diseases, Graduate School of Medicine, Kyoto University | en |
dc.identifier.pmid | 34108205 | - |
dc.relation.url | https://www.kyoto-u.ac.jp/ja/research-news/2021-06-10 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 19J22636 | - |
datacite.awardNumber | 18H02394 | - |
datacite.awardNumber | 17K08264 | - |
datacite.awardNumber | 19H05776 | - |
datacite.awardNumber | 19H05777 | - |
datacite.awardNumber | 15H05721 | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-19J22636/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-18H02394/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-17K08264/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-ORGANIZER-19H05776/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PLANNED-19H05777/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15H05721/ | - |
dc.identifier.pissn | 2375-2548 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.awardTitle | GPCRバイアスド・アゴニズム機構解明への構造生物学的アプローチと創薬への応用 | ja |
jpcoar.awardTitle | X線自由電子レーザーによるGタンパク質共役型受容体の活性化機構の解明 | ja |
jpcoar.awardTitle | シグナルを基軸としたGPCR作用薬のメカニズム解析 | ja |
jpcoar.awardTitle | 高速分子動画法によるタンパク質非平衡状態構造解析と分子制御への応用 | ja |
jpcoar.awardTitle | 光動作タンパク質の時分割構造解析と合理的改変 | ja |
jpcoar.awardTitle | CRISPRによるRNA病モデルiPS細胞・動物の構築と病態解明・治療薬創製 | ja |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
出現コレクション: | 学術雑誌掲載論文等 |
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