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

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

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.