ANP RECEPTOR STRUCTURE AND SIGNALING

ANP 受体结构和信号传导

基本信息

  • 批准号:
    7721196
  • 负责人:
  • 金额:
    $ 0.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-05-15 至 2009-03-31
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Atrial natriuretic peptide (ANP) is a cardiac hormone that stimulates salt excretion and dilates blood vessels. ANP plays a major role in blood pressure and salt-fluid volume regulation, and anomaly in its activities may cause heart failure, hypertension, and other cardiovascular diseases. ANP activities are mediated by a specific cell membrane receptor coupled to its intrinsic guanylate cyclase (GCase) activity. The receptor functions as a dimer of a single-span transmembrane protein, each consisting of an extracellular ANP-binding domain and an intracellular GCase catalytic domain. ANP binding to the extracellular domain activates GCase catalysis by an yet unknown mechanism. Our aims are to determine the structure of ANP receptor and to elucidate the mechanisms of receptor-hormone binding and transmembrane signaling. During the past year, we determined the crystal structure of the extracellular domain of the receptor (ANPR) in complex with the hormone ANP. By the structural comparison with the apo-receptor structure that we determined previously, we have identified a structural basis for ANP receptor signaling. We have found a unique hormone-induced rotation motion of the two juxtamembrane domains in the receptor dimmer that apparently initiates transmembrane signal transduction. Additionally, w have determine the crystal structure of the ANPR containing a non-covalently associated bromide ion (instead of chloride ion in the native receptor) (manuscript in preparation). We also have obtained preliminary structures of two constitutively active ANPR mutants. These studies will provide better understanding of the mechanism of ANP and ANP interaction, receptor activation, and regulation. Such knowledge will lead to more accurate diagnosis methods and effective treatments for cardiovascular diseases. These studies will also facilitate development of drugs targeted at the ANP receptor via structure-based drug design. Those drugs will be useful in treating heart failure, hypertension, and other cardiovascular diseases.An
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项目成果

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KUNIO S MISONO其他文献

KUNIO S MISONO的其他文献

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{{ truncateString('KUNIO S MISONO', 18)}}的其他基金

ANP RECEPTOR STRUCTURE AND SIGNALING
ANP 受体结构和信号传导
  • 批准号:
    7182908
  • 财政年份:
    2005
  • 资助金额:
    $ 0.7万
  • 项目类别:
ANP RECEPTOR STRUCTURE AND SIGNALING
ANP 受体结构和信号传导
  • 批准号:
    7369487
  • 财政年份:
    2005
  • 资助金额:
    $ 0.7万
  • 项目类别:
ANP RECEPTOR STRUCTURE AND SIGNALING
ANP 受体结构和信号传导
  • 批准号:
    6972747
  • 财政年份:
    2004
  • 资助金额:
    $ 0.7万
  • 项目类别:
NATRIURETIC PEPTIDE RECEPTOR--STRUCTURE AND SIGNALING
利尿钠肽受体——结构和信号传导
  • 批准号:
    2232676
  • 财政年份:
    1996
  • 资助金额:
    $ 0.7万
  • 项目类别:
NATRIURETIC PEPTIDE RECEPTOR--STRUCTURE AND SIGNALING
利尿钠肽受体——结构和信号传导
  • 批准号:
    2445300
  • 财政年份:
    1996
  • 资助金额:
    $ 0.7万
  • 项目类别:
NATRIURETIC PEPTIDE RECEPTOR--STRUCTURE AND SIGNALING
利尿钠肽受体——结构和信号传导
  • 批准号:
    2735259
  • 财政年份:
    1996
  • 资助金额:
    $ 0.7万
  • 项目类别:
Natriuretic peptide receptor: Structure and signaling
利钠肽受体:结构和信号传导
  • 批准号:
    6920588
  • 财政年份:
    1996
  • 资助金额:
    $ 0.7万
  • 项目类别:
Natriuretic peptide receptor: Structure and signaling
利钠肽受体:结构和信号传导
  • 批准号:
    6537183
  • 财政年份:
    1996
  • 资助金额:
    $ 0.7万
  • 项目类别:
Natriuretic peptide receptor: Structure and signaling
利钠肽受体:结构和信号传导
  • 批准号:
    6638409
  • 财政年份:
    1996
  • 资助金额:
    $ 0.7万
  • 项目类别:
Natriuretic peptide receptor: Structure and signaling
利钠肽受体:结构和信号传导
  • 批准号:
    6873038
  • 财政年份:
    1996
  • 资助金额:
    $ 0.7万
  • 项目类别:

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人胎盘心房利尿钠因子受体
  • 批准号:
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  • 财政年份:
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  • 财政年份:
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  • 批准号:
    3742522
  • 财政年份:
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  • 批准号:
    3868851
  • 财政年份:
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    $ 0.7万
  • 项目类别:
DEVELOPMENTAL STUDY OF VASCULAR ATRIAL NATRIURETIC FACTOR RECEPTORS
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