ヒトのシグナル伝達システムの発見:ペプチドとGタンパク質結合受容体の結合
Simon R Foster1, Alexander S Hauser1, Line Vedel1
1Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Cell
|November 2, 2019
まとめ
研究者はペプチドとGタンパク質結合受容体 (GPCRs) の間の新しい結合を特定し,人間のシグナル伝達システムの理解を広げました. この発見は 健康や病気における その役割に関する 将来の研究に道を開きます
科学分野:
- 人間の生理学と分子信号伝達
- ゲノミクスとバイオインフォマティクス
- 薬剤発見と受容体の薬理学
背景:
- リガンド受容体相互作用の広大なネットワークであるペプチド系は,多くのペプチドとGタンパク質結合受容体 (GPCR) が定義された生理学的役割を持たないため,まだ完全に理解されていません.
- 100以上のGタンパク質結合受容体 (GPCR) と多数のペプチドは未知の機能を持ち,ヒトの信号伝達経路の包括的な理解を妨げています.
研究 の 目的:
- 系統的に相性ペプチドと相応のGタンパク質結合受容体 (GPCRs) をペアリングする.
- 新しいペプチドシグナル伝達システムを特定し,既知のペプチドGPCRネットワークを拡張する.
- 孤児GPCRと疾患関連疾患を関連付けることで,潜在的な治療標的を明らかにする.
主な方法:
- 313種のゲノムを比較して 保存されたシグナル特性を特定する.
- ヒトのA級GPCR配列と構造のバイオ情報分析
- ペプチド-受容体のペアリングを検証する3つの直交生化学分析
主要な成果:
- 遺伝子,腫瘍,神経,生殖系疾患に関連した5つの孤児Gタンパク質結合受容体 (GPCRs) と17の提案された内生リガンドを成功裏にペアリングした.
- 9つのGタンパク質結合受容体 (GPCR) に対して,既知のリガンドと病理学的関連性を持つ追加のペプチドを特定した.
- 隠された普遍的な特徴は,追加の潜在的なペプチダージックシグナルシステムを示す.
結論:
- この統合された計算と実験的アプローチは,既知のヒトペプチドGPCRネットワークを大幅に拡張します.
- この発見は,ヒトの生理学と病気における,新たに特定されたシグナル伝達システムの役割を明らかにするための基礎を提供します.
- 以前は特徴づけられていなかったペプチダージック経路を標的とした治療の新たな道を開く.
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