APOLIPOPROTEIN E AND A 1 LIPID COMPLEX STRUCTURES
APOLIPOPROTEIN E AND A 1 LIPID COMPLEX STRUCTURES
批准号:
6390752
负责人:
KARL WEISGRABER
金额:
$35.85万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-04-01 至 2004-03-31
关键词:
X ray crystallography apolipoprotein E blood lipoprotein metabolism chemical models chemical structure function cholesterol crystallization enzyme induction /repression gene mutation lipid structure low density lipoprotein receptor molecular dynamics phosphatidylcholine sterol acyltransferase phosphatidylcholines receptor binding
中文摘要
载脂蛋白(Apo)E和apoA-1在细胞周期调控和细胞周期调控中发挥重要作用。
指导血浆脂蛋白代谢。任何一种蛋白质的功能障碍都会导致动脉粥样硬化增加,最终导致心脏病和中风。此外,apoE4是一种
已确定的神经退行性变和颅脑损伤预后不良的危险因素
还有中风。尽管载脂蛋白E和载脂蛋白A-1在正常生理中起着关键作用,
这些蛋白质中的任何一种都没有详细的结构信息
天然的脂质结合状态。这一建议是基于我们最近在结晶载脂蛋白-磷脂复合体方面的技术突破,旨在首次提供载脂蛋白E和载脂蛋白A-I与脂质结合的详细结构信息。三个具体目标侧重于与载脂蛋白E和载脂蛋白A-I的结构和功能有关的问题和问题。
1.载脂蛋白E-二肉豆蔻基磷脂酰胆碱(DMPC)络合物的结构
确定脂质结合如何影响载脂蛋白E功能。
2.假设apoA-1采用所谓的“带模式”构象。
将对磷脂圆盘进行测试,并了解其相互作用的结构细节
具有脂质和对LCAT激活的洞察的apoA-1两亲性螺旋将是
如果是这样的话。
3.分析胆固醇掺入磷脂的影响
ApoE和apoA-1结构上的盘状颗粒。
这些研究将为脂质的作用提供新的结构信息。
载脂蛋白E和载脂蛋白A-1的结构和功能的联系,并为
第一次,洞察这些蛋白质如何在其天然的
脂质相关状态。
英文摘要
Apolipoprotein (apo) E and apoA-1 play several critical roles in modulating and in
directing plasma lipoprotein metabolism. Dysfunction by either protein leads to increased atherosclerosis and ultimately to heart disease and stroke. In addition, apoE4 is an
established risk factor for neurodegeneration and poor outcome from head injury
and stroke. Despite the critical roles that apoE and apoA-1 play in normal physiology,
detailed structural information is not available for either of these proteins in their
natural lipid-bound state. This proposal is based on our recent technological breakthrough of crystalling apolipoprotein-phospholipid complexes and is designed to provide, for the first time, detailed structural information on apoE and apoA-I bound to lipid. Three specific aims focus on relevant issues and questions related to the structure and function of apoE and apoA-I.
1. The structures of apoE-dimyristoylphosphatidylcholine (DMPC) complexes will
be determined to ascertain how lipid association influences apoE function.
2. The hypothesis that apoA-1 adopts the so-called "belt model" conformation on
a phospholipid disc will be tested and structural details on the interaction of
apoA-1 amphipathic helices with lipid and insights into LCAT activation will be
provided.
3. To analyze the effect of cholesterol incorporation into phospholipid
discoidal particles on the structure of apoE and apoA-1.
These studies will provide novel structural information on the effect of lipid
association on the structure and function of apoE and apoA-1 and provide, for
the first time, insights into how these proteins function in their natural
lipid-associated state.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
PROTEIN STRUCTURE IN APOE4-ASSOCIATED NEURODEGENERATION
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批准号:7431631
-
项目类别:
-
资助金额:$35.05万
-
财政年份:2007
-
负责人:KARL WEISGRABER
-
依托单位:
SELENO METHIONINE INCORPORATION IN RECOMBINANT PROTEINS FOR XRAY CRYSTALLOGRAPH
-
批准号:7180913
-
项目类别:
-
资助金额:$0.47万
-
财政年份:2005
-
负责人:KARL WEISGRABER
-
依托单位:
SELENO METHIONINE INCORPORATION IN RECOMBINANT PROTEINS FOR XRAY CRYSTALLOGRAPHY
-
批准号:6976600
-
项目类别:
-
资助金额:$0.39万
-
财政年份:2004
-
负责人:KARL WEISGRABER
-
依托单位:
JEOL Transmission Electron Microscope
-
批准号:6731447
-
项目类别:
-
资助金额:$46.2万
-
财政年份:2004
-
负责人:KARL WEISGRABER
-
依托单位:
Role of ApoE4 Domain Interaction in Neurodegeneration
-
批准号:7005424
-
项目类别:
-
资助金额:$38.36万
-
财政年份:2002
-
负责人:KARL WEISGRABER
-
依托单位:
Role of ApoE4 Domain Interaction in Neurodegeneration
-
批准号:6421571
-
项目类别:
-
资助金额:$39.29万
-
财政年份:2002
-
负责人:KARL WEISGRABER
-
依托单位:
Role of ApoE4 Domain Interaction in Neurodegeneration
-
批准号:6620767
-
项目类别:
-
资助金额:$39.29万
-
财政年份:2002
-
负责人:KARL WEISGRABER
-
依托单位:
Protein Structure in ApoE4-associated Neurodegeneration
-
批准号:6562619
-
项目类别:
-
资助金额:$42.51万
-
财政年份:2002
-
负责人:KARL WEISGRABER
-
依托单位:
INFLUENCE OF APOLIPOPROTEIN E STRUCTURE ON FUNCTION
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批准号:6564894
-
项目类别:
-
资助金额:$23.92万
-
财政年份:2002
-
负责人:KARL WEISGRABER
-
依托单位:
Role of ApoE4 Domain Interaction in Neurodegeneration
-
批准号:6696338
-
项目类别:
-
资助金额:$39.29万
-
财政年份:2002
-
负责人:KARL WEISGRABER
-
依托单位:
Role of ApoE4 Domain Interaction in Neurodegeneration
-
批准号:6835132
-
项目类别:
-
资助金额:$39.29万
-
财政年份:2002
-
负责人:KARL WEISGRABER
-
依托单位:
INFLUENCE OF APOLIPOPROTEIN E STRUCTURE ON FUNCTION
-
批准号:6423872
-
项目类别:
-
资助金额:$23.92万
-
财政年份:2001
-
负责人:KARL WEISGRABER
-
依托单位:
APOLIPOPROTEIN E AND A 1 LIPID COMPLEX STRUCTURES
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批准号:6126943
-
项目类别:
-
资助金额:$38.81万
-
财政年份:2000
-
负责人:KARL WEISGRABER
-
依托单位:
APOLIPOPROTEIN E AND A 1 LIPID COMPLEX STRUCTURES
-
批准号:6638664
-
项目类别:
-
资助金额:$37.88万
-
财政年份:2000
-
负责人:KARL WEISGRABER
-
依托单位:
APOLIPOPROTEIN E AND A 1 LIPID COMPLEX STRUCTURES
-
批准号:6537836
-
项目类别:
-
资助金额:$36.85万
-
财政年份:2000
-
负责人:KARL WEISGRABER
-
依托单位:
INFLUENCE OF APOLIPOPROTEIN E STRUCTURE ON FUNCTION
-
批准号:6314118
-
项目类别:
-
资助金额:$28.53万
-
财政年份:2000
-
负责人:KARL WEISGRABER
-
依托单位:
SELENO METHIONINE INCORPORATION IN RECOMBINANT PROTEINS FOR XRAY CRYSTALLOGRAPHY
-
批准号:6308860
-
项目类别:
-
资助金额:$0.99万
-
财政年份:2000
-
负责人:KARL WEISGRABER
-
依托单位:
INFLUENCE OF APOLIPOPROTEIN E STRUCTURE ON FUNCTION
-
批准号:6109953
-
项目类别:
-
资助金额:$28.53万
-
财政年份:1999
-
负责人:KARL WEISGRABER
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依托单位:
SELENO METHIONINE INTO PROTEINS FOR XRAY CRYSTALLOGRAPHY: HEART DIS, ALZHEIMERS
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批准号:6120261
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项目类别:
-
资助金额:$0.11万
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财政年份:1999
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负责人:KARL WEISGRABER
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依托单位:
STRUCTURAL AND PHYSICAL BIOCHEMICAL ANALYSIS OF APOLIPOPROTEIN E
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批准号:6272856
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项目类别:
-
资助金额:$25.47万
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财政年份:1998
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负责人:KARL WEISGRABER
-
依托单位:
海外基金