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 在调节和
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加剧,并最终导致心脏病和中风。此外,apoE4 是
已确定的神经退行性变和头部损伤预后不良的危险因素
和中风。尽管 apoE 和 apoA-1 在正常生理学中发挥着关键作用,
这些蛋白质的详细结构信息均不可用
天然脂质结合状态。该提案基于我们最近在结晶载脂蛋白-磷脂复合物方面取得的技术突破,旨在首次提供与脂质结合的 apoE 和 apoA-I 的详细结构信息。三个具体目标集中于与 apoE 和 apoA-I 的结构和功能相关的相关问题和问题。
1. apoE-二肉豆蔻酰磷脂酰胆碱 (DMPC) 复合物的结构
确定脂质关联如何影响 apoE 功能。
2. apoA-1采用所谓“带模型”构象的假设
将测试磷脂盘并了解其相互作用的结构细节
具有脂质的 apoA-1 两亲性螺旋和对 LCAT 激活的见解将
提供。
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影响提供新的结构信息。
apoE 和 apoA-1 结构和功能的关联并提供
第一次深入了解这些蛋白质如何在其自然状态下发挥作用
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
-
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
-
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
-
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:
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: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:
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
-
依托单位:
SELENO METHIONINE INTO PROTEINS FOR XRAY CRYSTALLOGRAPHY: HEART DIS, ALZHEIMERS
-
批准号:6120261
-
项目类别:
-
资助金额:$0.11万
-
财政年份:1999
-
负责人:KARL WEISGRABER
-
依托单位:
STRUCTURAL AND PHYSICAL BIOCHEMICAL ANALYSIS OF APOLIPOPROTEIN E
-
批准号:6272856
-
项目类别:
-
资助金额:$25.47万
-
财政年份:1998
-
负责人:KARL WEISGRABER
-
依托单位:
海外基金