メタボトロピックGABAB受容体の構造
Makaía M Papasergi-Scott1,2, Michael J Robertson1,2, Alpay B Seven1,2
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|June 25, 2020
まとめ
メタボトロピック γ-アミノバター酸 (GABA) B受容体
科学分野:
- 神経科学
- 分子生物学
- 構造生物学
背景:
- メタボトロピックGABAB受容体は,脳における神経伝達抑制に極めて重要です.
- GABA B受容体は,Gタンパク質結合受容体Cファミリー内のユニークな結合ヘテロダイマーである.
- GABA B受容体の構造を理解することは,そのシグナル伝達メカニズムを解読する鍵です.
研究 の 目的:
- 凍結電子顕微鏡を用いてGABA B受容体の機能の構造的基礎を解明する.
- GABA B受容体信号伝達における細胞外ループ2 (ECL2) の役割を調査する.
- GABA B受容体を標的とした合理的な薬剤設計の洞察を提供するためです.
主な方法:
- 完全長さのGABAB受容体構造を決定するために,冷凍電子顕微鏡 (冷凍EM) を使用する.
- 細胞シグナリングアッセイで受容体の活性が評価される.
- 分子相互作用を分析するための原子模擬.
主要な成果:
- ヘテロディメアおよびホモディメアGABAB受容体の冷凍EM構造が得られた.
- 細胞外ループ2 (ECL2) は,リガンド結合からGタンパク質結合コアへの構造変化の伝達において重要な役割を果たします.
- ECL2は,トランスメブラン領域内のフォスフォリピドと相互作用し,リガンド結合をGタンパク質活性化に結びつける.
結論:
- この研究は,GABA B受容体信号伝達を理解するための構造的枠組みを提供します.
- この発見は,GABA B受容体の機能におけるECL2とフォスフォリピドの相互作用の重要な役割を強調しています.
- これらの洞察は神経疾患の標的治療の開発に不可欠です
さらに関連する動画
関連する概念動画
G Protein-coupled Receptors
15.9K
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...
15.9K
Activation and Inactivation of G Proteins
10.2K
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...
10.2K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.5K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.5K
Transducer Mechanism: G Protein–Coupled Receptors
3.6K
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,...
GPCRs are also called heptahelical,...
3.6K
G-protein Coupled Receptors
130.9K
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.
130.9K
G-Protein Gated Ion Channels
5.4K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
5.4K


