Mass spectrometric studies on potassium channels
Mass spectrometric studies on potassium channels
批准号:
6620406
负责人:
Adrian Gross
金额:
$14.7万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-12-10 至 2004-11-30
关键词:
Xenopus oocyte alkylation binding sites cysteine electrospray ionization mass spectrometry high performance liquid chromatography intermolecular interaction mass spectrometry membrane structure potassium channel protein structure protein structure function site directed mutagenesis structural biology technology /technique development
中文摘要
描述(由申请人提供):电压依赖性离子通道是
有助于产生膜电位、受体电位和
动作电位它们是分子构建模块,
神经科学中许多细胞的基本特征:兴奋性。这些
蛋白质参与所有兴奋性神经元的生理学和病理生理学。
组织,是许多疾病过程的基础,包括癫痫和心律失常,
是临床用药的主要靶点。尽管
这些蛋白质的明显生物学和临床重要性,我们仍然知道,
对它的结构知之甚少。虽然取得了重大进展,
在理解钾离子通道的离子渗透时,
这些必需的蛋白质在结构上仍然没有得到解决。
该提案探索了一种解决结构性问题的新技术
包括离子通道和其他膜蛋白。我们将使用一个组合
半胱氨酸扫描诱变,烷基化,和质谱研究
两个钾通道KcsA和Shaker的结构方面。我们称之
新技术如定点质量标记。长期目标是
建议是提供有关功能的低分辨率结构信息,
离子通道这项建议是高风险的,因为我们还不知道
这项技术是否会发挥其潜力,并证明是一个有用的
结构工具。如果成功的话,定位标记也许能够
为了解许多罕见的膜的总体结构提供了重要的见解
proteins.预计这项研究的结果将提供新的
深入了解振动筛的总体结构布局。
英文摘要
DESCRIPTION (provided by applicant): Voltage-dependent ion channels are
instrumental in the generation of membrane potential, receptor potential, and
action potential. They are the molecular building blocks for what is an
essential characteristic of many cells in neuroscience: excitability. These
proteins are implicated in the physiology and pathophysiology of all excitable
tissues, underlie many disease processes including epilepsies and arrhythmias,
and are major targets of essential drugs used in clinical medicine. Despite the
obvious biological and clinical importance of these proteins, we still know
relatively little about their structure. Although important progress has been
made in understanding ion permeation in potassium channels, large parts of
these essential proteins remain structurally unresolved.
This proposal explores a novel technique for addressing structural questions
involving ion channels and other membrane proteins. We will use a combination
of cysteine scanning mutagenesis, alkylation, and mass spectrometry to study
structural aspects of two potassium channels, KcsA and Shaker. We refer to this
novel technique as site-directed mass tagging. The long-term goal of this
proposal is to provide low-resolution structural information about functional
ion channels. The proposal is high risk in the sense that we do not yet know
whether the technique will fulfill its potential and prove to be a useful
structural tool. If successful, however, site-directed mass tagging may be able
to provide important insight into the gross structure of many rare membrane
proteins. It is anticipated that results from this study will provide new
insight into the general structural layout of Shaker.
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会议论文
Structural Studies on Prokaryotic Potassium Channels
-
批准号:7924176
-
项目类别:
-
资助金额:$10.63万
-
财政年份:2009
-
负责人:Adrian Gross
-
依托单位:
FAB-KCSA COMPLEX WITH THIOL LABELS
-
批准号:6978095
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2004
-
负责人:Adrian Gross
-
依托单位:
Mass spectrometric studies on potassium channels
-
批准号:6416760
-
项目类别:
-
资助金额:$14.7万
-
财政年份:2001
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:7075355
-
项目类别:
-
资助金额:$27.17万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:8396381
-
项目类别:
-
资助金额:$32.2万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
-
批准号:6628886
-
项目类别:
-
资助金额:$18.21万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
-
批准号:6151234
-
项目类别:
-
资助金额:$18.36万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:6967305
-
项目类别:
-
资助金额:$27.83万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
-
批准号:6442859
-
项目类别:
-
资助金额:$17.17万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:8305877
-
项目类别:
-
资助金额:$20.21万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:8638013
-
项目类别:
-
资助金额:$33.37万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
-
批准号:2729613
-
项目类别:
-
资助金额:$19.22万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:8197591
-
项目类别:
-
资助金额:$33.37万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:7250247
-
项目类别:
-
资助金额:$26.39万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
Structural Studies on Prokaryotic Potassium Channels
-
批准号:8042469
-
项目类别:
-
资助金额:$12.99万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
-
批准号:6498797
-
项目类别:
-
资助金额:$17.68万
-
财政年份:1999
-
负责人:Adrian Gross
-
依托单位:
STRUCTURE OF THE POTASSIUM CHANNEL CORE DOMAIN
-
批准号:2770854
-
项目类别:
-
资助金额:$1.72万
-
财政年份:1998
-
负责人:Adrian Gross
-
依托单位:
STRUCTURE OF THE POTASSIUM CHANNEL CORE DOMAIN
-
批准号:2415100
-
项目类别:
-
资助金额:$3.35万
-
财政年份:1998
-
负责人:Adrian Gross
-
依托单位:
海外基金