750MHz Wide Bore NMR Spectrometer

描述（由申请人提供）：本申请申请资金用于购买宽孔径750 MHz核磁共振（NMR）光谱仪，用于膜蛋白，大分子组装体和蛋白质聚集体的固态研究。固态核磁共振（SSNMR）是了解嵌入在生物膜内或形成大聚集体和组装体的蛋白质结构和动力学的重要工具。与其他结构方法相比，SSNMR的优势在于它不需要蛋白质形成晶体或可溶，并且可以在大于100 kD的蛋白质组装上进行。由于大匹兹堡地区缺乏专用的高场SSNMR仪器，越来越多地限制了他们在多个生物医学前沿的研究，因此拟议的收购解决了匹兹堡大学（University of Pittsburgh）的多名研究人员及其跨多所大学的合作者不断扩大的需求。新仪器将被安置在匹兹堡大学结构生物系最先进的核磁共振设备中，该部门是医学院最近成立的结构生物系的一部分。该仪器将满足多个合作网络中科学家的需求，包括美国国立卫生研究院支持的匹兹堡HIV蛋白相互作用中心（PCHPI）。将其并入现有的设备齐全的研究中心，将确保这一尖端仪器的最佳使用。所要求的仪器的主要用户将是匹兹堡大学医学院和特拉华大学，另外还有卡内基梅隆大学、巴克内尔大学和其他地方的用户（总共12组）。美国国立卫生研究院资助的多个研究项目将受益于这种专用的高场固态核磁共振光谱仪，包括研究与hiv细胞蛋白质相互作用、神经退行性疾病、神经递质和激素受体以及细胞运输有关的蛋白质和蛋白质组装。该仪器将完全配备固态多维光谱，专门用于均匀，广泛和选择性同位素（13C, 15N, 2H, 19F）富集的蛋白质，肽和大分子组件的3D结构测定和动力学分析。该仪器将配备低温装置和探针，以提高灵敏度，允许研究蛋白质折叠和反应中间体以及全面的动力学研究。探针和双接收器功能将使新的实验和数据采集协议的发展，以促进大蛋白质和蛋白质组装的研究。这台750 MHz SSNMR仪器将对匹兹堡大学和参与机构的基础设施产生直接影响，因为它将使尖端科学成为可能，将促进高度协作的生物医学研究，并将支持宾夕法尼亚州充满活力的研究环境。

DESCRIPTION (provided by applicant): This request is for funds to acquire a wide bore 750 MHz nuclear magnetic resonance (NMR) spectrometer for solid-state investigations of membrane proteins, macromolecular assemblies, and protein aggregates. Solid-state NMR (SSNMR) is an essential tool for understanding the structures and dynamics of proteins that are embedded within biological membranes or that form large aggregates and assemblies. An advantage of SSNMR, over other structural methods, is that it does not require proteins to form crystals or be soluble, and can be conducted on protein assemblies greater than 100 kD in size. The proposed acquisition addresses the expanding needs of multiple researchers at the University of Pittsburgh and their collaborators across multiple universities, as the lack of dedicated high-field SSNMR instrumentation in the greater Pittsburgh area is increasingly limiting their research on multiple biomedical fronts. The new instrument will be housed in the state-of-the art NMR facility in the Department of Structural Biology at the University of Pittsburgh - part of a recently established Department of Structural Biology at the School of Medicine. The instrument will serve the needs of scientists in multiple collaborative networks, including the NIH-supported Pittsburgh Center for HIV Protein Interactions (PCHPI). Its incorporation into a pre-existing and otherwise well-equipped research center will ensure optimal usage of this cutting-edge instrument. The major users of the requested instrument will be at the University of Pittsburgh School of Medicine and the University of Delaware, with additional users at Carnegie Mellon University, Bucknell University and elsewhere (12 groups in total). Multiple NIH-funded research projects will benefit from the availability of this dedicated high-field solid-state NMR spectrometer, including studies of proteins and protein assemblies involved in HIV-cellular protein interactions, neurodegenerative disorders, neurotransmitter and hormone receptors, as well as cellular trafficking. The instrument will be fully outfitted for multidimensional spectroscopy in the solid state, specifically for 3D structure determination and dynamics analysis of uniformly, extensively and selectively isotopically (13C, 15N, 2H, 19F) enriched proteins, peptides, and macromolecular assemblies. The instrument will be equipped with low temperature setup and probes, permitting investigations of protein folding and reaction intermediates as well as comprehensive dynamics studies, at enhanced sensitivity. The probes and the dual receiver capabilities will enable development of novel experiments and data acquisition protocols to facilitate studies of large proteins and protein assemblies. This 750 MHz SSNMR instrument will have an immediate impact on the infrastructure at the University of Pittsburgh and participating institutions as it will enable cutting-edge science, will foster highl collaborative biomedical research, and will support the vibrant research environment in the State of Pennsylvania.