STRUCTURAL CHANGE IN THE BETA SUBUNIT DURING GATING OF THE MUSCLE NICOTINIC RECEP

肌肉烟碱受体门控过程中 β 亚基的结构变化

基本信息

  • 批准号:
    8130871
  • 负责人:
  • 金额:
    $ 18.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-09-01 至 2013-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Members of the Cys-loop family of transmitter-gated ion channels are pentameric membrane proteins that respond to the binding of transmitter with a conformational change resulting in the opening of a gate and an increased affinity to the agonist. The muscle-type nicotinic acetylcholine receptor (nAChR) has served as a prototype in Cys-loop ion channel research due to its large single-channel conductance resulting in a high signal-to-noise ratio, and the relatively simple kinetic properties. In the nAChR, the two transmitter binding sites are located in the extracellular domain of the receptor at the interfaces between an a and a d subunit, and an a and an e. The subunit in the fifth position (b) is not directly involved in transmitter binding. The focus of this proposal is the non-transmitter-binding b subunit. We will use a combination of molecular biological, electrophysiological, and kinetic analyses approaches to determine the energetics and timing of gating motions in: i) the second membrane-spanning domain, ii) the extracellular region, and iii) the region comprising the linker between the second and third membrane-spanning regions and the pre-TM1 region. The work will elucidate the involvement of the b subunit in the conformational changes that lead to channel activation, and provide insight into the sources of molecular motions in the non- transmitter-binding subunit. The completion of the proposed work will increase our understanding of how transmitter-gated ion channels function, and how the non-transmitter-binding subunit shapes receptor function. PUBLIC HEALTH RELEVANCE: The nicotinic acetylcholine receptor mediates fast synaptic transmission in the vertebrate neuromuscular junction. The pentameric protein contains two transmitter binding sites located at subunit-subunit interfaces. This project is aimed at elucidating the role of the fifth subunit, which is not involved in transmitter binding, in the structural motions resulting in channel gating.
描述(由申请人提供):递质门控离子通道的Cys-loop家族成员是五聚体膜蛋白,它们对递质结合做出反应,产生构象变化,导致门的打开和对激动剂的亲和力增加。肌肉型尼古丁乙酰胆碱受体(nictinicacetylcholine receptor, nAChR)因其单通道电导大,信噪比高,且动力学性质相对简单,成为Cys-loop离子通道研究的原型。在nAChR中,两个递质结合位点位于受体的胞外结构域,位于a和d亚基以及a和e之间的界面。位于第5个位置(b)的亚基不直接参与递质结合。本提案的重点是非传递体结合的b亚基。我们将结合使用分子生物学、电生理学和动力学分析方法来确定门控运动的能量学和时间:i)第二跨膜区域,ii)细胞外区域,以及iii)包含第二和第三跨膜区域与前tm1区域之间连接的区域。这项工作将阐明b亚基参与导致通道激活的构象变化,并提供对非递质结合亚基分子运动来源的见解。这项工作的完成将增加我们对递质门控离子通道功能的理解,以及非递质结合亚基如何塑造受体功能。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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GUSTAV AKK其他文献

GUSTAV AKK的其他文献

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{{ truncateString('GUSTAV AKK', 18)}}的其他基金

GABAA receptors: function, physiology and involvement in anesthesia
GABAA 受体:功能、生理学和麻醉作用
  • 批准号:
    10406999
  • 财政年份:
    2021
  • 资助金额:
    $ 18.62万
  • 项目类别:
GABAA receptors: function, physiology and involvement in anesthesia
GABAA 受体:功能、生理学和麻醉作用
  • 批准号:
    10620344
  • 财政年份:
    2021
  • 资助金额:
    $ 18.62万
  • 项目类别:
GABAA receptors: function, physiology and involvement in anesthesia
GABAA 受体:功能、生理学和麻醉作用
  • 批准号:
    10582956
  • 财政年份:
    2021
  • 资助金额:
    $ 18.62万
  • 项目类别:
SYNERGISTIC ACTIONS OF INTRAVENOUS ANESTHETICS
静脉麻醉药的协同作用
  • 批准号:
    9319277
  • 财政年份:
    2014
  • 资助金额:
    $ 18.62万
  • 项目类别:
SYNERGISTIC ACTIONS OF INTRAVENOUS ANESTHETICS
静脉麻醉药的协同作用
  • 批准号:
    9111943
  • 财政年份:
    2014
  • 资助金额:
    $ 18.62万
  • 项目类别:
SYNERGISTIC ACTIONS OF INTRAVENOUS ANESTHETICS
静脉麻醉药的协同作用
  • 批准号:
    10058841
  • 财政年份:
    2014
  • 资助金额:
    $ 18.62万
  • 项目类别:
SYNERGISTIC ACTIONS OF INTRAVENOUS ANESTHETICS
静脉麻醉药的协同作用
  • 批准号:
    8758980
  • 财政年份:
    2014
  • 资助金额:
    $ 18.62万
  • 项目类别:
INSECTICIDE ACTIONS ON NICOTINIC ACETYLCHOLINE RECEPTORS
对烟碱乙酰胆碱受体的杀虫作用
  • 批准号:
    8025983
  • 财政年份:
    2010
  • 资助金额:
    $ 18.62万
  • 项目类别:
INSECTICIDE ACTIONS ON NICOTINIC ACETYLCHOLINE RECEPTORS
对烟碱乙酰胆碱受体的杀虫作用
  • 批准号:
    7788661
  • 财政年份:
    2010
  • 资助金额:
    $ 18.62万
  • 项目类别:
INSECTICIDE ACTIONS ON NICOTINIC ACETYLCHOLINE RECEPTORS
对烟碱乙酰胆碱受体的杀虫作用
  • 批准号:
    8072489
  • 财政年份:
    2010
  • 资助金额:
    $ 18.62万
  • 项目类别:

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