New methods development for structure determination of multihelical membrane proteins in their native-like lipid bilayers by solid-state NMR with applications

通过固态核磁共振确定多螺旋膜蛋白天然脂质双层结构的新方法及其应用

• 批准号: 1508400
• 负责人: Alexander Nevzorov
• 金额: $ 40万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1508400&HistoricalAwards=false
• 关键词: New; methods; development; structure; determination

In this Project funded by the Chemical Measurement and Imaging program of the Chemistry Division, Professor Alexander Nevzorov is studying membrane proteins (MPs) under their native-like conditions by solid-state Nuclear Magnetic Resonance (NMR) spectroscopy. Membrane proteins perform a plethora of biological functions, yet the number of their solved structures remains relatively small. The solid-state NMR technique allows researchers to perform structure-function studies of MPs that are difficult or impossible to crystallize at nearly physiological conditions. NMR spectroscopic methods developed during this research expand capabilities of this technique to multihelical MPs.The main purpose of this project is to transform solid-state NMR of oriented membrane proteins (MPs) by developing new spectroscopic tools including methods for distance measurements and assignment of crowded spectral regions. Moreover, new membrane mimetics of flexible lipid composition based on nanopores and oriented macrodisks are being created to monitor lipid-induced conformational changes of MPs. Dynamic properties of lipid bilayers are probed including rotational diffusion of membrane-embedded proteins and the bilayer viscosity. Potential future applications include structure determination of the human Acetylcholine receptor involved in the Alzheimer's disease and other neurological disorders. As broader impacts of this project, the highly interdisciplinary nature of this research provides versatile training for the young scientists involved. As outreach activities, via mentorship of a Kenan Fellow, Dr. Nevzorov promotes the results of his research to high-school education and STEM programs.

在这个由化学部化学测量和成像项目资助的项目中，Alexander Nevzorov 教授正在通过固态核磁共振 (NMR) 光谱研究类似天然条件下的膜蛋白 (MP)。膜蛋白具有多种生物学功能，但其已解析结构的数量仍然相对较少。固态核磁共振技术使研究人员能够对在接近生理条件下难以或不可能结晶的 MP 进行结构功能研究。 本研究期间开发的核磁共振波谱方法将该技术的能力扩展到多螺旋 MP。该项目的主要目的是通过开发新的波谱工具（包括距离测量和拥挤分配方法）来改变定向膜蛋白（MP）的固态核磁共振。光谱区域。此外，基于纳米孔和定向宏盘的柔性脂质成分的新膜模拟物正在被创建，以监测脂质诱导的 MP 构象变化。探讨了脂质双层的动态特性，包括膜嵌入蛋白质的旋转扩散和双层粘度。未来的潜在应用包括与阿尔茨海默病和其他神经系统疾病有关的人类乙酰胆碱受体的结构测定。作为该项目更广泛的影响，这项研究的高度跨学科性质为参与的年轻科学家提供了多样化的培训。作为外展活动，在凯南研究员的指导下，内夫佐罗夫博士将他的研究成果推广到高中教育和 STEM 项目。