| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-10-30 |
| タイトル |
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タイトル |
Structural basis for lysophosphatidylserine recognition by GPR34 |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Izume, Tamaki
Kawahara, Ryo
Uwamizu, Akiharu
Luying, Chen
Yaginuma, Shun
Omi, Jumpei
川名, 裕己
Hou, Fengjue
Sano, Fumiya K
Tanaka, Tatsuki
Kobayashi, Kazuhiro
Okamoto, Hiroyuki H.
Kise, Yoshiaki
Ohwada, Tomohiko
Aoki, Junken
Shihoya, Wataru
Nureki, Osamu
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-Gi complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34. |
| 書誌情報 |
en : Nature communications
巻 15,
号 1,
ページ数 15,
発行日 2024-02-07
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| 出版者 |
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出版者 |
Nature Research |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
2041-1723 |
| 出版者版DOI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1038/s41467-024-45046-z |
| 出版者版URI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
URI |
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関連識別子 |
https://www.nature.com/articles/s41467-024-45046-z |
| 権利 |
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権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
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権利情報 |
© The Author(s) 2024.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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/ licenses/by/4.0/. |
| 著者版フラグ |
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出版タイプ |
NA |
| 助成情報 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
21H05037 |
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研究課題番号URI |
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-22K19371/ |
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研究課題名 |
生体環境でのGPCRの構造ダイナミクス |
| 助成情報 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
22K19371 |
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研究課題番号URI |
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-22K19371/ |
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研究課題名 |
リゾリン脂質受容体を標的としたGPCR創薬2.0 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
22H02751 |
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研究課題番号URI |
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-23K24014/ |
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研究課題名 |
クライオ電子顕微鏡法を用いたGPCR創薬研究 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
22H00438 |
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研究課題番号URI |
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-22H00438/ |
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研究課題名 |
リゾリン脂質メディエーターの新規免疫制御機構の解明とその薬学的意義 |
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助成機関名 |
ONO Medical Research Foundation |
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助成機関名 |
Kao Foundation for Arts and Sciences |
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助成機関名 |
Takeda Science Foundation |
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助成機関名 |
Uehara Memorial Foundation |
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助成機関名 |
Lotte Foundation |
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助成機関名 |
Kobayashi Foundation |
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助成機関名 |
KOSÉ Cosmetology Research Foundation |
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助成機関名 |
Japan Agency for Medical Research and Development（AMED） |
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研究課題番号 |
JP233fa627001 |
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研究課題名 |
ワクチン開発のための世界トップレベル研究開発拠点群 東京フラッグシップキャンパス(東京大学新世代感染症センター) |
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助成機関名 |
Japan Agency for Medical Research and Development（AMED） |
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研究課題番号 |
22ck0106533h0003 |
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研究課題名 |
がん免疫におけるリゾリン脂質シグナルの意義解明とリゾリン脂質受容体を標的とした抗がん剤開発 |
| 助成情報 |
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助成機関名 |
Japan Agency for Medical Research and Development（AMED） |
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研究課題番号 |
21gm0010004h9905 |
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研究課題名 |
リゾリン脂質メディエーター研究の医療応用 |
| 助成情報 |
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助成機関名 |
Japan Agency for Medical Research and Development (AMED) |
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研究課題番号 |
JP22ama121002 |
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研究課題名 |
クライオ電子顕微鏡による分子・細胞構造解析の支援と高度化 |
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助成機関名 |
Japan Agency for Medical Research and Development (AMED) |
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研究課題番号 |
JP22ama121012 |
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研究課題名 |
高難度膜タンパク質等の調製と構造解析可能なグリッド調製の支援 |
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助成機関名 |
Otsuka Toshimi Scholarship Foundation |
