Structure and Dynamics of the Influenza M2 Protein and Plant Cell Walls Determined by Solid-State NMR Spectroscopy

Seminar: Physical Chemistry | March 21 | 4-5 p.m. |  Pitzer Auditorium, 120 Latimer Hall

 Prof. Mei Hong, Department of Chemistry, MIT

 College of Chemistry

High-resolution solid-state NMR spectroscopy is a powerful and versatile method to determine, at atomic resolution, the structure, mobility, and intermolecular interactions of biomolecules in their native environments, thus giving rich insights into the mechanisms of action of biomolecules. I will present our studies of the influenza virus M2 protein and plant cell walls to illustrate this point. M2 is a multifunctional protein of influenza viruses: it serves as a proton channel during virus entry into cells and mediates membrane scission during virus budding. Using 13C, 15N, 1H, 2H, and 19F NMR, we have elucidated the proton conduction mechanism of the M2 channels of both influenza A and B viruses, showing that a key histidine residue in the transmembrane domain forms a mixed hydrogen-bonded chain with water molecules to actively shuttle protons into the virion. The rates, equilibrium dissociation constants, sidechain motions, ring tautomerization, and cation-π interactions of this proton shuttling process have been measured. We determined where the antiviral drug, amantadine, binds in the influenza A M2 channel, and how binding interferes with proton shuttling of histidine.

In the second project, we bring multidimensional SSNMR to bear on plant cell walls, a complex polysaccharide-rich material that provides mechanical strength to plant cells while allowing plant cells to expand rapidly during plant growth. Because of their insoluble nature, plant cell walls have long been resistant to molecular-level structural characterization. By growing entire plants in 13C-enriched media and harvesting the intact primary cell walls in a hydrated state, we are able to measure 2D and 3D correlation SSNMR spectra of whole cell walls that revealed how cellulose, hemicellulose and pectins interact with each other in model plants of both dicot (Arabidopsis thaliana) and monocot (Brachypodium distachyon) families, how plant cellulose structure differs from bacterial cellulose, and what the minimum size of cellulose microfibrils is in plant cell walls. Finally, using sensitivity-enhancing dynamic nuclear polarization NMR approaches, we determined how a protein, expansin, binds the wall polysaccharide to loosen the cell wall during plant growth.

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