プロカリオットとユカリオットのカリウムチャネルにおける構造保存
R MacKinnon1, S L Cohen, A Kuo
1Laboratory of Molecular Neurobiology and Biophysics and the Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. mackinn@rockvax.rockefeller.edu
Science (New York, N.Y.)
|April 29, 1998
まとめ
の毒の毒素は,細菌のカリウムチャネル (K+チャネル) に対してスクリーニングされました. 研究者らは,プロカリオットK+チャネルがユーカリオットと構造的類似性を共有し,K+チャネル薬剤発見の新たな道を開いていることを発見しました.
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:
- カリウムチャネル (K+チャネル) は,多くの生理学的プロセスに関与する重要なトランスメブランタンパク質です.
- スコーピオンの毒は様々な毒素を含み,しばしばK+チャネルを含むイオンチャネルを標的にします.
- K+チャネル構造と機能を理解することは,治療薬の開発に不可欠です.
研究 の 目的:
- カリウムチャネルと相互作用する毒素を探すために,の毒をスクリーニングします.
- プロカリオットとユカリオットのK+チャネル間の構造的保存を調査する.
- K+チャネル薬理学の新しいアプローチを確立する.
主な方法:
- 高通量スクリーニングのために,Streptomyces lividansの樹脂付属の変異K+チャネルを使用した.
- K+チャネルと相互作用する毒の毒素を迅速に特定するために,質量スペクトロメトリーを使用した.
- 特定の毒素チャネル相互作用を特徴付けるために,変異変異と放射性リガンド結合アッセイを実施しました.
主要な成果:
- 細菌のK+チャネルに対するLeiurus quinquestriatus hebraeusの毒を成功裏にスクリーニングしました.
- K+チャネルに結合するアジトキシン2を含む特定の毒素を特定した.
- プロカリオットK+チャネルは,ユーカリオットK+チャネルで保存された孔構造を有することを実証した.
結論:
- プロカリオットK+チャネルは,ユーカリオットK+チャネル構造を研究するための貴重なモデルとして機能します.
- 開発されたスクリーニングと特徴付け技術は,K+チャネル薬剤発見のための新しいプラットフォームを提供します.
- 構造的保存は,K+チャネル薬理学における広範な応用の可能性を強調しています.
関連する概念動画
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.
01:19The Role of Ion Channels in Neuronal Computation
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.
01:26Voltage-gated Ion Channels
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
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...
01:24Non-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.
01:26Voltage-gated Ion Channels
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...