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Angew Chem Int Ed Engl. 2017 Apr 4. doi: 10.1002/anie.201701874. [Epub ahead of print]
Activation pH and Gating Dynamics of Influenza A M2 Proton Channel Revealed by Single-Molecule Spectroscopy.
Lin CW1, Mensa B2, Barniol-Xicota M2, DeGrado WF2, Gai F1,3.
Author information
Abstract
Because of its importance in viral replication, the M2 proton channel of the influenza A virus has been the focus of many studies. Although we now know a great deal about the structural architecture underlying its proton conduction function, we know little about its conformational dynamics, especially those controlling the rate of this action. Herein, we employ a single-molecule fluorescence method to assess the dynamics of the inter-helical channel motion of both full-length M2 and the transmembrane domain of M2. The rate of this motion depends not only on the identity of the channel and membrane composition but also on the pH in a sigmoidal manner. For the full-length M2 channel, the rate is increased from approximately 190 μs-1 at high pH to approximately 80 μs-1 at low pH, with a transition midpoint at pH 6.1. Because the latter value is within the range reported for the conducting pKa value of the His37 tetrad, we believe that this inter-helical motion accompanies proton conduction.
? 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
KEYWORDS:
M2 proton channels; conformational dynamics; fluorescence correlation spectroscopy; pH titration; photoinduced electron transfer
PMID: 28374543 DOI: 10.1002/anie.201701874
Activation pH and Gating Dynamics of Influenza A M2 Proton Channel Revealed by Single-Molecule Spectroscopy.
Lin CW1, Mensa B2, Barniol-Xicota M2, DeGrado WF2, Gai F1,3.
Author information
Abstract
Because of its importance in viral replication, the M2 proton channel of the influenza A virus has been the focus of many studies. Although we now know a great deal about the structural architecture underlying its proton conduction function, we know little about its conformational dynamics, especially those controlling the rate of this action. Herein, we employ a single-molecule fluorescence method to assess the dynamics of the inter-helical channel motion of both full-length M2 and the transmembrane domain of M2. The rate of this motion depends not only on the identity of the channel and membrane composition but also on the pH in a sigmoidal manner. For the full-length M2 channel, the rate is increased from approximately 190 μs-1 at high pH to approximately 80 μs-1 at low pH, with a transition midpoint at pH 6.1. Because the latter value is within the range reported for the conducting pKa value of the His37 tetrad, we believe that this inter-helical motion accompanies proton conduction.
? 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
KEYWORDS:
M2 proton channels; conformational dynamics; fluorescence correlation spectroscopy; pH titration; photoinduced electron transfer
PMID: 28374543 DOI: 10.1002/anie.201701874