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Hydrogen-Bonding Partner of the Proton-Conducting Histidine in the Influenza M2 Proton Channel Revealed From 1H Chemical Shifts
- Hong, Mei, Fritzsching, Keith J., Williams, Jonathan K.
- Journal of the American Chemical Society 2012 v.134 no.36 pp. 14753-14755
- ambient temperature, histidine, hydrogen bonding, influenza, models, nuclear magnetic resonance spectroscopy, pH, protons, virion
- The influenza M2 protein conducts protons through a critical histidine (His) residue, His37. Whether His37 only interacts with water to relay protons into the virion or whether a low-barrier hydrogen bond (LBHB) also exists between the histidines to stabilize charges before proton conduction is actively debated. To address this question, we have measured the imidazole ¹Hᴺ chemical shifts of His37 at different temperatures and pH using 2D ¹⁵N–¹H correlation solid-state NMR. At low temperature, the Hᴺ chemical shifts are 8–15 ppm at all pH values, indicating that the His37 side chain forms conventional hydrogen bonds (H-bonds) instead of LBHBs. At ambient temperature, the dynamically averaged Hᴺ chemical shifts are 4.8 ppm, indicating that the H-bonding partner of the imidazole is water instead of another histidine in the tetrameric channel. These data show that His37 forms H-bonds only to water, with regular strength, thus supporting the His–water proton exchange model and ruling out the low-barrier H-bonded dimer model.