Structure of the Human Cannabinoid Receptor
人类大麻素受体的结构
基本信息
- 批准号:6901807
- 负责人:
- 金额:$ 3.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-11-01 至 2005-10-30
- 项目状态:已结题
- 来源:
- 关键词:G proteinSDS polyacrylamide gel electrophoresisactive sitescannabinoid receptorcell linecrosslinkendopeptidasesenzyme structuregene mutationligandsmembrane proteinspredoctoral investigatorprotein engineeringprotein foldingprotein protein interactionprotein sequenceprotein structure functionwestern blottings
项目摘要
DESCRIPTION (provided by applicant):
The main objective of this proposal is to learn about the structure of the helical bundle, which makes up the integral membrane portion and the ligand-binding site of the human cannabinoid receptor (CB1). Understanding the helix-helix interactions within the bundle will help to elucidate the residues involved in the ligand-binding pocket, information that is crucial for further development of therapeutics. The aims of the proposal are to identify transmembrane domains that drive the assembly of CB1 from fragments, and to identify helical regions involved in these interactions. Receptors will be generated that incorporate sites for recognition by specific proteases, expressed in HEK 293 cells and proteolytically cleaved to produce large fragments. Retention of the native form will be determined by ligand binding and G protein activation assays and will serve to identify stabilizing interhelical associations between the fragments. The interacting surfaces will be more precisely mapped via cysteine disulfide crosslinking. These studies will improve our understanding of how interacting transmembrane segments are arranged in the helical bundle in order to orchestrate receptor assembly, ligand binding and receptor activation. This information can then be applied to the development of selective therapeutics and drugs to antagonize the ill effects of marijuana.
描述(由申请人提供):
该提案的主要目的是了解螺旋束的结构,该结构构成了人类大麻素受体(CB 1)的完整膜部分和配体结合位点。了解束内的螺旋-螺旋相互作用将有助于阐明参与配体结合口袋的残基,这对进一步开发治疗方法至关重要。该提案的目的是确定跨膜结构域,驱动组件的CB 1片段,并确定螺旋区域参与这些相互作用。将产生受体,其包含用于被特定蛋白酶识别的位点,在HEK 293细胞中表达并被蛋白水解切割以产生大片段。天然形式的保留将通过配体结合和G蛋白活化测定来确定,并将用于鉴定片段之间的稳定化螺旋间缔合。相互作用的表面将通过半胱氨酸二硫化物交联更精确地映射。这些研究将提高我们的理解如何相互作用的跨膜段排列在螺旋束,以协调受体组装,配体结合和受体活化。这些信息可以应用于选择性治疗和药物的开发,以对抗大麻的不良影响。
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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AARON M D'ANTONA其他文献
AARON M D'ANTONA的其他文献
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{{ truncateString('AARON M D'ANTONA', 18)}}的其他基金
Structural and Biochemical Studies of the Metarhodopsin II-Transducin Complex
后视紫红质 II-转导蛋白复合物的结构和生化研究
- 批准号:
7485350 - 财政年份:2008
- 资助金额:
$ 3.79万 - 项目类别: