Magic-Angle-Spinning NMR
of the Drug Resistant S31N
M2 Proton Transporter from Influenza A
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Abstract
We report chemical shift assignments of the drug-resistant
S31N
mutant of M2<sub>18–60</sub> determined using 3D magic-angle-spinning
(MAS) NMR spectra acquired with a <sup>15</sup>N–<sup>13</sup>C ZF-TEDOR transfer followed by <sup>13</sup>C–<sup>13</sup>C mixing by RFDR. The MAS spectra reveal two sets of resonances,
indicating that the tetramer assembles as a dimer of dimers, similar
to the wild-type channel. Helicies from the two sets of chemical shifts
are shown to be in close proximity at residue H37, and the assignments
reveal a difference in the helix torsion angles, as predicted by TALOS+,
for the key resistance residue N31. In contrast to wild-type M2<sub>18–60</sub>, chemical shift changes are minimal upon addition
of the inhibitor rimantadine, suggesting that the drug does not bind
to S31N M2