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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10798817
• 关键词: 2019-nCoV; ABCB1 gene; Antibiotics; Bacteria; Bacterial Infections; Binding; Binding Sites; Cell Nucleus; E protein; Fluorine; Geometry; Human; Influenza; Influenza B Virus; Ion Channel; Life Cycle Stages; M2 protein; Measurement; Membrane; Membrane Lipids; Membrane Proteins; Molecular; Pharmaceutical Preparations; Proteins; Resolution; Sampling; Signal Transduction; Speed; Structure; Viral; Virus; Virus Diseases; bacterial resistance; design; env Gene Products; experimental study; future pandemic; influenza M2; membrane assembly; mutant; nanometer; pathogen; prevent; radio frequency; restraint; small molecule; solid state nuclear magnetic resonance

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.

项目总结

项目成果

Effects of amantadine on the dynamics of membrane-bound influenza A M2 transmembrane peptide studied by NMR relaxation.

• DOI: 10.1007/s10858-009-9352-9
• 发表时间: 2009-09
• 期刊: Journal of biomolecular NMR
• 影响因子: 2.7
• 作者: Cady SD;Hong M
• 通讯作者: Hong M

Relaxation-compensated difference spin diffusion NMR for detecting 13C-13C long-range correlations in proteins and polysaccharides.

• DOI: 10.1007/s10858-014-9889-0
• 发表时间: 2015-02
• 期刊: Journal of biomolecular NMR
• 影响因子: 2.7
• 作者: Wang T;Williams JK;Schmidt-Rohr K;Hong M
• 通讯作者: Hong M

(15)N and (1)H Solid-State NMR Investigation of a Canonical Low-Barrier Hydrogen-Bond Compound: 1,8-Bis(dimethylamino)naphthalene.

典型低势垒氢键化合物的 (15)N 和 (1)H 固态 NMR 研究：1,8-双(二甲氨基)萘。

• DOI: 10.1021/acs.jpcb.5b06171
• 发表时间: 2015
• 期刊: The journal of physical chemistry. B
• 作者: White,PaulB;Hong,Mei
• 通讯作者: Hong,Mei

pH-dependent conformation, dynamics, and aromatic interaction of the gating tryptophan residue of the influenza M2 proton channel from solid-state NMR.

• DOI: 10.1016/j.bpj.2013.02.054
• 发表时间: 2013-04
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: Jonathan K. Williams;Y. Zhang;K. Schmidt-Rohr;M. Hong

The Influenza M2 Ectodomain Regulates the Conformational Equilibria of the Transmembrane Proton Channel: Insights from Solid-State Nuclear Magnetic Resonance.

流感 M2 胞外域调节跨膜质子通道的构象平衡：来自固态核磁共振的见解。

• DOI: 10.1021/acs.biochem.6b00727
• 发表时间: 2016
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Kwon,Byungsu;Hong,Mei
• 通讯作者: Hong,Mei