Structural Insights into TRPV Channel Gating

TRPV 通道选通的结构见解

• 批准号: 10204495
• 负责人: Vera Moiseenkova-Bell
• 金额: $ 15.19万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204495
• 关键词: Award; Cell membrane; Computing Methodologies; Cryoelectron Microscopy; Cytoskeleton; Drug Targeting; Electrophysiology (science); Event; Future; Human; Human body; Immunity; Ions; Ligands; Lipids; Molecular; Parents; Phosphatidylinositols; Physiological; Physiology; Play; Regulation; Role; Site-Directed Mutagenesis; Structure; TRP channel; TRPV channel; Therapeutic; Vanilloid; antitumor drug; design; heart function; insight; receptor

PROJECT SUMMARY/ABSTRACT (parent award) Transient receptor potential (TRP) channels play significant roles in human physiology and facilitate essential ions’ (Na+, Ca2+) permeation through the plasma membrane. The focus of this proposal is on the transient receptor potential vanilloid 2 (TRPV2), which plays an essential role in cardiac function and immunity, and has been placed on the list of important anti-tumor drug targets. Nevertheless, it remains the least studied TRPV channel at the cellular and molecular levels. We propose to use the combination of cryo-EM, electrophysiological analysis, site-directed mutagenesis, and computational methods to establish a detailed structural understanding of the mechanisms of TRPV2 channel gating. In this current proposal we will focus on understanding TRPV2 regulation by phosphoinositides, determine the mechanism of TRPV2 gating by diverse ligands and dissect the molecular mechanism of TRPV2 interaction with cytoskeleton. Information obtained upon completion of these studies will be potentially used for future design of TRPV2 specific therapeutics

项目概要/摘要（母公司奖） 瞬时受体电位（TRP）通道在人体生理学中起着重要作用， 促进必需离子（Na+、Ca ~（2+））透过质膜。的重点 该提案是关于瞬时受体电位香草素2（TRPV 2），它在 在心功能和免疫方面具有重要作用，已被列入重要的抗肿瘤药物名单 目标的尽管如此，它仍然是在细胞和分子水平上研究最少的TRPV通道。 程度.我们建议使用冷冻电镜，电生理分析，定点 诱变，和计算方法，以建立一个详细的结构理解的 TRPV 2通道门控机制。在目前的提案中，我们将重点关注理解 通过磷酸肌醇调节TRPV 2，确定TRPV 2门控的机制， 配体，并剖析TRPV 2与细胞骨架相互作用的分子机制。信息 完成这些研究后获得的数据将有可能用于TRPV 2的未来设计 特效药

项目成果

Structure of thermally activated TRP channels.

• DOI: 10.1016/b978-0-12-800181-3.00007-5
• 发表时间: 2014
• 期刊: CURRENT TOPICS IN MEMBRANES
• 作者: Cohen, Matthew R.;Moiseenkova-Bell, Vera Y.
• 通讯作者: Moiseenkova-Bell, Vera Y.

Transient Receptor Potential (TRP) Channels.

• DOI: 10.1007/978-981-10-7757-9_6
• 发表时间: 2018
• 期刊: Sub-cellular biochemistry
• 作者: Samanta A;Hughes TET;Moiseenkova-Bell VY
• 通讯作者: Moiseenkova-Bell VY

Application of amphipols for structure-functional analysis of TRP channels.

• DOI: 10.1007/s00232-014-9684-6
• 发表时间: 2014-10
• 期刊: JOURNAL OF MEMBRANE BIOLOGY
• 影响因子: 2.4
• 作者: Huynh, Kevin W.;Cohen, Matthew R.;Moiseenkova-Bell, Vera Y.
• 通讯作者: Moiseenkova-Bell, Vera Y.