在 prokaryotic 和 eukaryotic 通道中的结构性保护
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
概括
对子毒素的毒素进行了对细菌通道 (K+通道) 的选. 研究人员发现, prokaryotic K + 通道与真核细胞的结构相似,为 K + 通道药物发现开辟了新的途径.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 通道 (K+通道) 是关键的跨膜蛋白质,参与许多生理过程.
- 子毒含有多种毒素,通常准离子通道,包括K+通道.
- 了解K+通道结构和功能对于开发治疗剂至关重要.
研究的目的:
- 为了选与通道相互作用的毒素的子毒液.
- 研究 prokaryotic 和 eukaryotic K+ 通道之间的结构保护.
- 建立K+通道药理学的新方法.
主要方法:
- 利用来自Streptomyces lividans的树脂附着,突变的K+通道进行高通量查.
- 使用质谱仪快速识别与K+通道相互作用的毒毒素.
- 进行了突变发生和放射性体结合试验,以表征特定的毒素通道相互作用.
主要成果:
- 成功选了来自Leiurus quinquestriatus hebraeus的毒液,以对抗细菌的K+通道.
- 确定了特定的毒素,包括与K+通道结合的激素2,这些毒素与K+通道结合.
- 证明原生细胞K+通道具有与真核细胞K+通道保持的孔隙结构.
结论:
- Prokaryotic K+ 通道作为研究真核 K+ 通道结构的有价值模型.
- 开发的查和表征技术为K+通道药物发现提供了一个新的平台.
- 结构性保护突出了在K+通道药理学中广泛应用的潜力.
相关概念视频
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...