750MHz Wide Bore NMR Spectrometer

描述(申请人提供)：申请资金用于购买一台大口径750 MHz核磁共振(核磁共振)光谱仪，用于对膜蛋白质、大分子组件和蛋白质聚集体进行固态研究。固态核磁共振是了解嵌入在生物膜中或形成大聚集和组装的蛋白质的结构和动力学的重要工具。与其他结构方法相比，SS核磁共振的一个优点是它不需要蛋白质形成晶体或可溶，并且可以在大小超过100kD的蛋白质组件上进行。这项拟议的收购满足了匹兹堡大学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，因为大匹兹堡地区缺乏专用的高场SS核磁共振仪器，越来越限制了他们在多个生物医学前沿的研究。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施中--这是最近在医学院成立的结构生物学系的一部分。该仪器将服务于多个合作网络中的科学家的需求，包括美国国立卫生研究院支持的匹兹堡艾滋病毒蛋白质相互作用中心(PCHPI)。它被整合到一个预先存在的、设备齐全的研究中心，将确保这一尖端仪器的最佳使用。申请的仪器的主要用户将在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(共12组)。NIH资助的多个研究项目将受益于这种专用高场固态核磁共振光谱仪的供应，包括对涉及艾滋病毒-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贩运的蛋白质和蛋白质组件的研究。该仪器将配备齐全的固态多维光谱，特别是用于均匀、广泛和选择性地同位素(13C、15N、2H、19F)浓缩的蛋白质、多肽和大分子组件的3D结构测定和动力学分析。该仪器将配备低温装置和探头，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。探头和双接收器能力将使新的实验和数据采集协议的开发成为可能，以促进对大型蛋白质和蛋白质组件的研究。这台750 MHz SS核磁共振仪将对匹兹堡大学和参与机构的基础设施产生立竿见影的影响，因为它将促进尖端科学，促进高度合作的生物医学研究，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.