アセチルコリン受容体孔の構造とゲーティング機構
Atsuo Miyazawa1, Yoshinori Fujiyoshi, Nigel Unwin
1RIKEN Harima Institute, 1-1-1 Kouto, Mikazuki-cho, Sayo, Hyogo 679-5148, Japan.
Nature
|June 27, 2003
まとめ
閉じたニコチンアセチルコリン受容体孔の原子構造を明らかにし,神経と筋肉のコミュニケーションのための重要なチャネルです. アセチルコリン結合は,水害性ゲートを破壊することによって,毛孔の開口を誘発します.
科学分野:
- 神経科学は神経科学である.
- 構造生物学 構造生物学とは
- バイオフィジックス 生物物理学
背景:
- ニコチンアセチルコリン受容体 (nAChR) は,神経系および神経筋の交差点での高速なシナプス伝達に不可欠です.
- それはリガンドゲートイオンチャネルとして機能し,細胞膜を横断するイオンの流れを制御します.
- nAChRの構造,特にその毛孔を理解することは,そのゲートメカニズムを解読し,標的治療を開発するために不可欠です.
研究 の 目的:
- ニコチンアセチルコリン受容体ポールの閉じた状態の原子レベルの構造を決定する.
- nAChR内のイオン浸透とゲーティングの構造的基礎を解明する.
- nAChR関数を理解するための高解像度モデルを提供する.
主な方法:
- 結晶型ポストシナプス膜の電子顕微鏡.
- 受容体の毛穴領域の原子モデル再構築.
- 孔内のアルファヘリケスの配置と相互作用の分析.
主要な成果:
- 閉じたnAChR孔の原子模型が生成されました.
- 毛穴は5つのアルファヘリクスの内輪と15個のアルファヘリクスの外輪で構成されています.
- 内部ヘリクスの相互作用によって形成された水嫌性帯は,脂質二重層の真ん中のゲートとして作用します.
結論:
- 構造は,内部のヘリクによって並べられ,外部のヘリクによって遮断された,縮小するイオン経路を明らかにします.
- リガンド結合は,水害性帯を壊し,イオンチャネルを開く形状の変化を誘導します.
- これは,nAChRチャネルゲーティングの詳細な構造メカニズムを提供します.
関連する概念動画
COP Coated Vesicles
Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of different...
Structure of Porins
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
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...
Structure of Cadherins
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Tight Junctions
Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
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...


