课题基金 / 基金详情

PERMEABILITY CONTROL OF ACETYLCHOLINE RECEPTOR

PERMEABILITY CONTROL OF ACETYLCHOLINE RECEPTOR
乙酰胆碱受体的通透性控制
批准号:
6094354
负责人:
JONATHAN Brewer COHEN
金额:
$5.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1982
资助国家:
美国
项目状态:
已结题
起止时间:
1982-09-01 至 2001-11-30

项目摘要

项目成果

JONATHAN Brewer COHEN的其他基金

相似基金

相关文献

中文摘要
翻译
我们希望了解烟碱型乙酰胆碱受体(AChR)是如何 作为配基门控离子通道的功能,并理解药物和 毒素与AChR相互作用,改变其功能。鱼雷电动 组织将被分割成。分离要使用的突触后膜 在生物化学研究中,旨在:1)识别功能域 (配体结合部位,离子通道)与已知氨基酸的关系 AChR亚基的序列并鉴定其结构的差异 那些区分激动剂和激动剂结合的区域 拮抗剂或AChR的不同构象状态之间,以及 2)提供对的三维结构的一般描述 细胞外暴露的每个亚基区域的乙酰胆碱受体 或细胞质表面,在亚单位界面,或与脂质接触。 放射性标记的亲和标记和结构探针将共价 整合到AChR中,并标记AChR亚单位将被分离和 降解,以便标记的位置将由N-末端确定 分离的标记肽的序列分析。结构研究 将提供特定氨基酸和包含的区域的定义 在结合部位、亚单位界面或蛋白质-脂类之间 接口,但它们自己并不评估 确定氨基酸是配体结合亲和力的决定因素或 它们参与了通道门控的机制。要解决这些问题 问题的第三个研究目标是测试AChR结构衍生的模型 从结构研究出发,通过分析其功能特性 突变型AChRs在非洲爪哇卵母细胞中的表达。平衡约束 激动剂和拮抗剂的亲和力将通过放射性配基进行评估 结合分析,而AChR功能将通过 电生理技术。点突变将被引入到 氨基酸变化预计对配体结合亲和力很重要 或用于通道门控,其他突变将由氨基组成 预测在结构变化的传播中很重要的酸 从ACh结合部位到离子通道。
英文摘要
We wish to understand how the nicotinic acetylcholine receptor (AChR) functions as a ligand-gated ion channel and to understand how drugs and toxins interact with the AChR to alter its function. Torpedo electric tissue will be fractionated to. isolate postsynaptic membranes to be used in biochemical studies designed to: 1) identify functional domains (ligand binding sites, ion channel) in terms of the known amino acid sequences of AChR subunits and to identify differences in structure of those domains that distinguish between the binding of agonists and antagonists or between different conformational states of the AChR, and 2) provide a general description of the three dimensional structure of the AChR in terms of the regions of each subunit exposed at extracellular or cytoplasmic surfaces, at subunit interfaces, or in contact with lipid. Radiolabeled affinity labels and structural probes will be covalently incorporated into AChR, and labeled AChR subunits will be isolated and degraded so that sites of labeling will be determined by N-terminal sequence analysis of isolated labeled peptides. The structural studies will provide a definition of particular amino acids and regions contained within binding sites, at subunit interfaces, or at the protein- lipid interface, but they do not of their own assess the importance of the identified amino acids as determinants of ligand binding affinity or their involvement in the mechanism of channel gating. To address these issues a third research goal is to test models of AChR structure derived from the structural studies by analysis of functional properties of mutant AChRs expressed in Xenopus oocytes. The equilibrium binding affinity of agonists and antagonists will be assessed by radioligand binding assays, while AChR function will be assessed by electrophysiological techniques. Point mutations will be introduced to change amino acids predicted to be important for ligand binding affinity or for channel-gating, and additional mutations will be made of amino acids predicted to be important in the propagation of structural changes from the ACh binding site to the ion channel.
期刊论文(26)
专著(0)
科研奖励(0)
会议论文
Interactions between 3-(Trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine and tetracaine, phencyclidine, or histrionicotoxin in the Torpedo series nicotinic acetylcholine receptor ion channel.
鱼雷系列烟碱乙酰胆碱受体离子通道中 3-(三氟甲基)-3-(间-[(125)I]碘苯基)二氮丙啶与丁卡因、苯环利定或组烟毒素之间的相互作用。
DOI: 10.1124/mol.59.6.1514
发表时间: 2001
期刊: Molecular pharmacology
影响因子: 3.6
作者: [Gallagher,MJ, Chiara,DC, Cohen,JB]
通讯作者: Cohen,JB
DOI: 10.1074/jbc.275.17.12651
发表时间: 2000
期刊: The Journal of biological chemistry
影响因子: --
作者: [Sullivan,DA, Cohen,JB]
通讯作者: Cohen,JB
Agonist-induced changes in the structure of the acetylcholine receptor M2 regions revealed by photoincorporation of an uncharged nicotinic noncompetitive antagonist.
不带电荷的烟碱非竞争性拮抗剂的光掺入揭示了激动剂诱导的乙酰胆碱受体 M2 区域结构的变化。
DOI: --
发表时间: 1992
期刊: The Journal of biological chemistry
影响因子: --
作者: [White,BH, Cohen,JB]
通讯作者: Cohen,JB
Kinetics of binding of [3H]acetylcholine and [3H]carbamoylcholine to Torpedo postsynaptic membranes: slow conformational transitions of the cholinergic receptor.
[3H]乙酰胆碱和[3H]氨基甲酰胆碱与鱼雷突触后膜结合的动力学:胆碱能受体的缓慢构象转变。
DOI: 10.1021/bi00564a031
发表时间: 1980
期刊: Biochemistry
影响因子: 2.9
作者: [Boyd,ND, Cohen,JB]
通讯作者: Cohen,JB
共 13 条
    Project 1: Locating General Anesthetic Binding Sites in GABAA & Acetylcholine Rec
    • 批准号:
      8137268
    • 项目类别:
    • 资助金额:
      $30.26万
    • 财政年份:
      2010
    • 负责人:
      JONATHAN Brewer COHEN
    • 依托单位:
    Project 1: Locating General Anesthetic Binding Sites in GABAA & Acetylcholine Rec
    • 批准号:
      7777109
    • 项目类别:
    • 资助金额:
      $29.7万
    • 财政年份:
      2009
    • 负责人:
      JONATHAN Brewer COHEN
    • 依托单位:
    Core C: Protein Chemistry Core
    • 批准号:
      7777114
    • 项目类别:
    • 资助金额:
      $28.52万
    • 财政年份:
      2009
    • 负责人:
      JONATHAN Brewer COHEN
    • 依托单位:
    LOCATING GENERAL ANESTHETIC SITES IN ACETYCHOLINE RECEPTORS
    • 批准号:
      6564606
    • 项目类别:
    • 资助金额:
      $13.16万
    • 财政年份:
      2001
    • 负责人:
      JONATHAN Brewer COHEN
    • 依托单位:
    海外基金