Gタンパク質結合受容体の構造と機能について
Daniel M Rosenbaum1, Søren G F Rasmussen, Brian K Kobilka
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Palo Alto, California 94305, USA.
Nature
|May 22, 2009
まとめ
Gタンパク質結合受容体 (GPCRs) は,生理学的反応と疾患治療において極めて重要です. 最近の構造研究は,GPCRの活性化と構成活動に関する洞察を明らかにしています.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 薬理学 薬理学とは
背景:
- Gタンパク質結合受容体 (GPCRs) は,多くの生理学的プロセスに関与する細胞表面受容体である.
- それらは,ホルモン,神経伝達物質,環境刺激に対する反応を媒介する役割があるため,現代の治療法の重要な部分のターゲットです.
- GPCRsを理解することは,さまざまな病気の治療法を開発する上で鍵となるものです.
研究 の 目的:
- Gタンパク質結合受容体 (GPCRs) の理解における最近の進歩を要約します.
- 膜タンパク質構造と生物学におけるGPCRの重要性を強調する.
- GPCRの活性化メカニズムに関する高解像度構造研究から得られた洞察を探求する.
主な方法:
- 薬理学的データのレビュー.
- 機能的特徴化研究 in vivo. 機能的特徴化研究 in vivo.
- 最近の高解像度構造データの分析.
主要な成果:
- 過去30年間,GPCRの薬理学とインビヴォ機能の理解において,著しい進展がみられた.
- 高解像度の構造研究は,GPCR活性化の分子メカニズムを明らかにしました.
- GPCRの構成活動に関する洞察は,構造生物学を通じて得られた.
結論:
- GPCRsは,さまざまな疾患の重要な治療標的を代表しています.
- 構造生物学における進歩は,GPCRの機能に関する深い洞察を提供します.
- GPCRsに関する継続的な研究は,将来の薬物開発に希望を示しています.
関連する概念動画
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...


