Magic Angle Spinning NMR Investigation of Influenza A M2(18-60): Support for an Allosteric Mechanism of Inhibition
Author(s)Andreas, Loren; Eddy, Matthew Thomas; Pielak, Rafal M.; Chou, James; Griffin, Robert Guy
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The tetrameric M2 proton channel from influenza A virus conducts protons at low pH and is inhibited by aminoadamantyl drugs such as amantadine and rimantadine (Rmt). We report magic angle spinning NMR spectra of POPC and DPhPC membrane-embedded M2[subscript 18−60], both apo and in the presence of Rmt. Similar line widths in the spectra of apo and bound M2 indicate that Rmt does not have a significant impact on the dynamics or conformational heterogeneity of this construct. Substantial chemical shift changes for many residues in the transmembrane region support an allosteric mechanism of inhibition. An Rmt titration supports a binding stoichiometry of >1 Rmt molecule per channel and shows that nonspecific binding or changes in membrane composition are unlikely sources of the chemical shift changes. In addition, doubling of spectral lines in all of the observed samples provides evidence that the channel assembles with twofold symmetry.
DepartmentMassachusetts Institute of Technology. Department of Chemistry; Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)
Journal of the American Chemical Society
American Chemical Society (ACS)
Andreas, Loren B. et al. “Magic Angle Spinning NMR Investigation of Influenza A M2[subscript 18−60]: Support for an Allosteric Mechanism of Inhibition.” Journal of the American Chemical Society 132.32 (2010): 10958–10960.
Author's final manuscript