title: Activation pH and Gating Dynamics of Influenza A M2 Proton Channel Revealed by Single-Molecule Spectroscopy.
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-1at high pH to approximately 80 μs-1at low pH, with a transition midpoint at pH 6.1. Because the latter value is within the range reported for the conducting pKavalue of the His37 tetrad, we believe that this inter-helical motion accompanies proton conduction.
authors.affiliation: Ultrafast Optical Processes Laboratory, Department of Chemistry, University of Pennsylvania, Philadelphia, 231 S. 34th Street, Philadelphia, PA, 19104, USA.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA, 94158-2517, USA.
authors.forename: Bruk
authors.initials: B
authors.lastname: Mensa
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA, 94158-2517, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Barniol-Xicota
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA, 94158-2517, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
authors.affiliation: Ultrafast Optical Processes Laboratory, Department of Chemistry, University of Pennsylvania, Philadelphia, 231 S. 34th Street, Philadelphia, PA, 19104, USA.|Department of Chemistry, University of Pennsylvania, Philadelphia, 231 S. 34th Street, Philadelphia, PA, 19104, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gai
mesh_terms: D004579:Electron Transport; D005456:Fluorescent Dyes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D055668:Photochemical Processes; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D005456:Fluorescent Dyes; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: M2 proton channels; conformational dynamics; fluorescence correlation spectroscopy; pH titration; photoinduced electron transfer