2つのGタンパク質に結合したクラスDのGPCR Ste2ダイマーの構造
Vaithish Velazhahan1, Ning Ma2, Gáspár Pándy-Szekeres3,4
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature
|December 3, 2020
まとめ
研究者は,活性状態の真菌のGタンパク質結合受容体 (GPCR) の構造を決定した. この発見は 治療が難しい真菌病と闘うための 新しい抗真菌薬の開発に 模範となるものです
科学分野:
- 構造生物学
- 生物化学
- 菌類学
背景:
- Gタンパク質結合受容体 (GPCR) は,細胞表面受容体として重要なもので,遺伝学的に6つのクラスに分類される.
- クラスA,B,C,Fの構造は知られているが,DクラスのGPCRは菌類に限定され,構造的には特徴づけられていない.
- 菌類DのGPCRは菌類の生存と繁殖を制御する上で重要な役割を果たします.
研究 の 目的:
- 活性構造のSaccharomyces cerevisiae (酵母) のクラスDのGPCRの構造を決定する.
- 菌類のGPCRにおけるGタンパク質結合の構造的基礎を解明する.
- キノコのGPCRを理解し,ターゲットにするための枠組みを確立する.
主な方法:
- ヘトロトリメリックGタンパク質 (Gpa1-Ste4-Ste18) と複合したSaccharomyces cerevisiaeフェロモン受容体の浄化.
- X線結晶学 (暗示) のようなテクニックを使用して,活性状態の構造を決定する.
- 比較分析のためのクラスD1の一般的な残留物番号システム (CD1) の開発.
主要な成果:
- 構造は,2つのGタンパク質に結合したホモディマーとしてSte2を明らかにする.
- 主要な構造的特徴は,N端によって形成されたダイマーインターフェース,特定のトランスメブランヘリックス (H1,H2,H7) およびECL1である.
- クラスAのGPCRと比較すると,H4のトランスメブランヘリックスがシフトし,明確な浅いGタンパク質結合槽が示される.
結論:
- これは,活性状態のクラスDのGPCRの最初の構造です.
- Ste2のようなキノコのGPCRのユニークな構造特性は,他のクラスとは異なる.
- 解明された構造は,病原菌に対する新しい治療法を設計するための青写真として役立つ.
さらに関連する動画
09:40Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
18.2K
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
9.2K
関連する概念動画
G-protein Coupled Receptors
129.3K
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.
129.3K
Transducer Mechanism: G Protein–Coupled Receptors
3.4K
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,...
3.4K
G Protein-coupled Receptors
15.3K
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...
15.3K
Activation and Inactivation of G Proteins
9.2K
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...
9.2K
Assembly of Signaling Complexes
6.3K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.3K
GPCR Desensitization
7.4K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
7.4K
