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Quadruple-resonance HFXY 1.3 mm CP-MAS probe for a solid-state NMR wide-bore magnet

用于固态 NMR 大口径磁体的四共振 HFXY 1.3 mm CP-MAS 探头

基本信息

批准号：
10798817
负责人：
Mei Hong
金额：
$ 19.75万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2025-06-30
项目状态：
未结题

项目摘要

Project Summary This proposal aims to elucidate the structures and mechanism of action of three ion channels and transporters of viruses and bacteria: the SARS-CoV-2 envelope (E) protein, the influenza M2 protein, and the multidrug-resistant bacterial transporter, EmrE. All three proteins form membrane-bound ion channels or transporters that are important for the lifecycle and function of the respective virus or bacteria. Molecular structural information about these membrane proteins forms the basis for designing antiviral and antibiotic compounds to prevent viral and bacterial infections. For all three membrane proteins, fluorine has been strategically incorporated into the proteins or the substrate to enable the measurement of nanometer distances by solid-state NMR. These distances are powerful restraints for the interhelical assembly of these membrane proteins and the protein-substrate binding-site structure. However, the current NMR probe in the Hong lab for these 19F-based NMR experiments is limited by the spinning speed and the availability of only one radiofrequency channel beside 1H and 19F. To obtain higher-resolution NMR spectra and to correlate 1H and 19F signals with multiple nuclei, we request an 1.3 mm HFXY probe that can spin samples to 65 kHz and that tunes to two heteronuclear channels (X and Y). Using this 1.3 mm HFXY probe, we will investigate the open-state structure of the SARS-CoV-2 E protein, the open-state structure of an influenza BM2 mutant, and the substrate-binding site geometry of the EmrE protein.

项目摘要这一建议旨在阐明三个离子的结构和作用机制。病毒和细菌的通道和转运体：SARS-CoV-2外壳(E)蛋白，流感M2蛋白和多药耐药细菌转运蛋白EmRE。所有这三种蛋白质形成膜结合的离子通道或转运体，对生命周期和各自的病毒或细菌的功能。关于这些的分子结构信息膜蛋白是设计抗病毒和抗生素化合物的基础，以防止病毒和细菌感染。对于所有三种膜蛋白，氟都是具有战略意义的加入到蛋白质或底物中，以实现纳米距离的测量通过固态核磁共振。这些距离是对这些螺旋间组装的强大限制膜蛋白和蛋白质-底物结合部位结构。然而，目前的核磁共振香港实验室中用于这些基于19F的核磁共振实验的探测器受到旋转速度和除1H和19F外，只有一个射频通道可用。要获得更高的分辨率核磁共振谱并将1H和19F信号与多核关联，我们需要1.3毫米HFXY 可以将样品旋转到65 kHz并调谐到两个异核通道(X和Y)的探测器。利用这个1.3 mm的HFXY探针，我们将研究SARS-CoV-2的开放状态结构 E蛋白，流感BM2突变体的开放状态结构和底物结合部位 Emre蛋白的几何结构。