探査イオンチャネルは,一度に1個の陽子を孔を開く
Gisela D Cymes1, Ying Ni, Claudio Grosman
1Department of Molecular and Integrative Physiology, Center for Biophysics and Computational Biology, and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Nature
|December 16, 2005
まとめ
研究者は,膜タンパク質内の電離可能な残留物の陽子化状態を正確に測定しました. これは,タンパク質機能とゲーティングメカニズムに影響を与えるマイクロ環境の詳細な地図を提供します.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 神経科学は神経科学である.
背景:
- 膜タンパク質は,重要な構造と機能のために,電離可能な残留物を利用します.
- 生理学的条件下でこれらの残留物のイオン化状態を決定することは,実験的に困難です.
研究 の 目的:
- 地元の微環境が,電離可能な残留物の陽子相性に対する影響を調査する.
- ニコチンアセチルコリン受容体のトランスメブラン孔内の残留特異的マイクロ環境の特徴づけ.
主な方法:
- M2トランスメブランアルファヘリックスに沿って,特殊なイオン化残留物 (ライシン,ヒスティジン,アルギニン) を設計した.
- 電子生理学を用いて,単一の陽子の結合-解き放たれをカチオン電流の変動として検出した.
- 位置依存型プロトン伝送率を決定し,pK (a) 値を計算するために,変動の運動分析を行った.
主要な成果:
- オープンチャネル状態のM2ヘリ周辺のマイクロ環境の残留分別エネルギー記述を開発しました.
- 機械廃棄物のプロトン化に必要な余分な自由エネルギーを,散発水と比較して定量化した.
- 閉じた状態と比較して,オープンチャネルの形状で最小のM2ヘリックス回転が見つかりました.
結論:
- この研究は,膜タンパク質の電離可能な残留物に影響を与える微環境の新しい高解像度マップを提供します.
- この発見は,Cysループ受容体における主要なゲーティングメカニズムとしての提案された有意なM2ヘリックス回転に異議を唱える.
- この方法論は,膜タンパク質の静電学とダイナミクスを研究するための強力なアプローチを提供します.
関連する概念動画
01:19Ion Channels
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
01:12Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
01:21G-Protein Gated Ion Channels
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 organs,...
Sensory organs,...
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
01:12Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...