Structure and Function of Nicotinic Receptors
烟碱受体的结构和功能
基本信息
- 批准号:6766367
- 负责人:
- 金额:$ 18.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-07-01 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:TorpedoXenopusXenopus oocyteacetylcholineallosteric sitediffusionelectrophysiologygene expressiongenetic regulationintermolecular interactionmembrane activitymembrane channelsmembrane lipidsmembrane structuremolecular assembly /self assemblynicotinic receptorsprotein structure functiontemperaturevoltage /patch clamp
项目摘要
Changes in the structure and function of the Nicotinic Acetylcholine Receptor (AChR) are linked to pathogenic responses on human muscle and brain. The long-range goal of this research proposal is to define the functional role of lipid-protein interactions in the conformational transitions of the AChR. The objective of this project is to define the modes by which lipid protein interactions are linked to the gating machinery of the AChR. The central hypothesis of this research is that AChR channel kinetics is modulated allosterically by specific sites on the
receptor that are in direct contact with the membrane lipids. This hypothesis has been formulated on the basis of strong preliminary data, which suggest that single amino acid replacements at discrete lipid-exposed positions on the M4 transmembrane segments of the AChR greatly enhanced the macroscopic response to acetylcholine. The rationale for the proposed research is that lipid-protein interactions could represent a very important mechanism for the regulation of AChR channel function in cholinergic synapses of the muscle and brain and understanding
the molecular basis of these mechanisms would help to identify conditions in which the impairment of AChR function can lead to disease. The central hypothesis will be tested and the objective of the application will be accomplished by pursuing three specific aims: (1) to define helix-helix contacts, structural constraint positions and additional allosteric sites of the muscle-type AChR, using periodic tryptophan substitutions along the M4 transmembrane domains, (2) Define the role of 11 lipid exposed positions on the functional differences between
the Torpedo and muscle-type AChR. (3) Perform Fluorescence Photobleaching Recovery (FRAP) to estimate translational diffusion measurements of AChRs of the Torpedo and muscle type AChRs in the plasmatic membrane of Xenopus oocytes. The proposed work is innovative because it capitalizes on new approaches developed by the applicants to estimate AChR translational diffusion constant in oocytes in vivo. It is our expectation that these approaches will define new mechanisms by which lipid-protein interactions that modulate
the allosteric transitions of AChR. The outcomes will be significant because it is expected that the new knowledge will disclose new mechanisms for AChR regulation in the intact synapse. This research will be of additional significance, because it will also provide information on the secondary structure and the spatial organization of the M4 transmembrane segment, as well as to the structure-function relationships of the AChR.
Another biological significance of this project is that it will provide new understanding of the role of lipid-exposed domains within the AChR and how such lipid-protein interactions can contribute to functional differences between AChR species. Analysis of the lipid-protein interactions of the AChR are not only important for understanding the functioning of ligand-gated ion channels, but may also provide insight into the mechanisms of action of certain therapeutic drugs, such as alcohols and general anesthetics.
烟碱乙酰胆碱受体(AChR)结构和功能的变化与人体肌肉和大脑的致病性反应有关。本研究计划的长期目标是确定脂质-蛋白相互作用在AChR构象转变中的功能作用。该项目的目的是确定脂质蛋白相互作用与乙酰胆酸受体的门控机制相关联的模式。本研究的中心假设是,乙酰胆碱受体通道动力学是由蛋白上的特定位点进行变构调节的
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JOSE Antonio LASALDE-DOMINICCI其他文献
JOSE Antonio LASALDE-DOMINICCI的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JOSE Antonio LASALDE-DOMINICCI', 18)}}的其他基金
UPR Center for Incubator and Technology Transfer (UPRCITT)
UPR 孵化器和技术转让中心 (UPRCITT)
- 批准号:
10793133 - 财政年份:2023
- 资助金额:
$ 18.7万 - 项目类别:
COBRE PHASE III: Center for Neuroplasticity at the University of Puerto Rico
COBRE 第三阶段:波多黎各大学神经可塑性中心
- 批准号:
10628974 - 财政年份:2023
- 资助金额:
$ 18.7万 - 项目类别:
COBRE Phase 2: Center for Neuroplasticity at the University of Puerto Rico
COBRE 第 2 阶段:波多黎各大学神经可塑性中心
- 批准号:
10798588 - 财政年份:2022
- 资助金额:
$ 18.7万 - 项目类别:
COBRE Phase 2: Center for Neuroplasticity at the University of Puerto Rico
COBRE 第 2 阶段:波多黎各大学神经可塑性中心
- 批准号:
10212399 - 财政年份:2013
- 资助金额:
$ 18.7万 - 项目类别:
A lipid-based approach towards a high-resolution structure of a functional nAChR
基于脂质的方法获得功能性 nAChR 的高分辨率结构
- 批准号:
9068277 - 财政年份:2013
- 资助金额:
$ 18.7万 - 项目类别:
A lipid-based approach towards a high-resolution structure of a functional nAChR
基于脂质的方法获得功能性 nAChR 的高分辨率结构
- 批准号:
8158503 - 财政年份:2013
- 资助金额:
$ 18.7万 - 项目类别:
A lipid-based approach towards a high-resolution structure of a functional nAChR
基于脂质的方法获得功能性 nAChR 的高分辨率结构
- 批准号:
8739659 - 财政年份:2013
- 资助金额:
$ 18.7万 - 项目类别:
COBRE Phase 2: Center for Neuroplasticity at the University of Puerto Rico
COBRE 第 2 阶段:波多黎各大学神经可塑性中心
- 批准号:
10449241 - 财政年份:2013
- 资助金额:
$ 18.7万 - 项目类别:
相似海外基金
TRANSLATIONAL REGULATION DURING XENOPUS OOCYTE DEVELOPMENT
非洲爪蟾卵母细胞发育过程中的翻译调控
- 批准号:
7610009 - 财政年份:2007
- 资助金额:
$ 18.7万 - 项目类别:
TRANSLATIONAL REGULATION DURING XENOPUS OOCYTE DEVELOPMENT
非洲爪蟾卵母细胞发育过程中的翻译调控
- 批准号:
7381391 - 财政年份:2006
- 资助金额:
$ 18.7万 - 项目类别:
CORE--ELECTROPHYSIOLOGY AND XENOPUS OOCYTE LABORATORY
核心--电生理学和爪蟾卵细胞实验室
- 批准号:
6575674 - 财政年份:2002
- 资助金额:
$ 18.7万 - 项目类别:
CORE--ELECTROPHYSIOLOGY AND XENOPUS OOCYTE LABORATORY
核心--电生理学和爪蟾卵细胞实验室
- 批准号:
6660036 - 财政年份:2002
- 资助金额:
$ 18.7万 - 项目类别:
CORE--ELECTROPHYSIOLOGY AND XENOPUS OOCYTE LABORATORY
核心--电生理学和爪蟾卵细胞实验室
- 批准号:
6441471 - 财政年份:2001
- 资助金额:
$ 18.7万 - 项目类别:
CORE--ELECTROPHYSIOLOGY AND XENOPUS OOCYTE LABORATORY
核心--电生理学和爪蟾卵细胞实验室
- 批准号:
6347434 - 财政年份:2000
- 资助金额:
$ 18.7万 - 项目类别:
UCP induction on the inner cell and mitochondrial membrances of Xenopus oocyte injected with gene transcripts from brown adipocytes of cold acclimated rat
注射冷驯化大鼠棕色脂肪细胞基因转录本的非洲爪蟾卵母细胞内细胞和线粒体膜上的 UCP 诱导
- 批准号:
12670069 - 财政年份:2000
- 资助金额:
$ 18.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CORE--ELECTROPHYSIOLOGY AND XENOPUS OOCYTE LABORATORY
核心--电生理学和爪蟾卵细胞实验室
- 批准号:
6301309 - 财政年份:2000
- 资助金额:
$ 18.7万 - 项目类别:
CORE--ELECTROPHYSIOLOGY AND XENOPUS OOCYTE LABORATORY
核心--电生理学和爪蟾卵细胞实验室
- 批准号:
6106113 - 财政年份:1999
- 资助金额:
$ 18.7万 - 项目类别: