Jump to main content
Jump to site search

Issue 41, 2016
Previous Article Next Article

Infrared and fluorescence assessment of the hydration status of the tryptophan gate in the influenza A M2 proton channel

Author affiliations

Abstract

The M2 proton channel of the influenza A virus has been the subject of extensive studies because of its critical role in viral replication. As such, we now know a great deal about its mechanism of action, especially how it selects and conducts protons in an asymmetric fashion. The conductance of this channel is tuned to conduct protons at a relatively low biologically useful rate, which allows acidification of the viral interior of a virus entrapped within an endosome, but not so great as to cause toxicity to the infected host cell prior to packaging of the virus. The dynamic, structural and chemical features that give rise to this tuning are not fully understood. Herein, we use a tryptophan (Trp) analog, 5-cyanotryptophan, and various methods, including linear and nonlinear infrared spectroscopies, static and time-resolved fluorescence techniques, and molecular dynamics simulations, to site-specifically interrogate the structure and hydration dynamics of the Trp41 gate in the transmembrane domain of the M2 proton channel. Our results suggest that the Trp41 sidechain adopts the t90 rotamer, the χ2 dihedral angle of which undergoes an increase of approximately 35° upon changing the pH from 7.4 to 5.0. Furthermore, we find that Trp41 is situated in an environment lacking bulk-like water, and somewhat surprisingly, the water density and dynamics do not show a measurable difference between the high (7.4) and low (5.0) pH states. Since previous studies have shown that upon channel opening water flows into the cavity above the histidine tetrad (His37), the present finding thus provides evidence indicating that the lack of sufficient water molecules near Trp41 needed to establish a continuous hydrogen bonding network poses an additional energetic bottleneck for proton conduction.

Graphical abstract: Infrared and fluorescence assessment of the hydration status of the tryptophan gate in the influenza A M2 proton channel

Back to tab navigation

Supplementary files

Publication details

The article was received on 19 May 2016, accepted on 22 Sep 2016 and first published on 22 Sep 2016


Article type: Paper
DOI: 10.1039/C6CP03426H
Citation: Phys. Chem. Chem. Phys., 2016,18, 28939-28950
  •   Request permissions

    Infrared and fluorescence assessment of the hydration status of the tryptophan gate in the influenza A M2 proton channel

    B. N. Markiewicz, T. Lemmin, W. Zhang, I. A. Ahmed, H. Jo, G. Fiorin, T. Troxler, W. F. DeGrado and F. Gai, Phys. Chem. Chem. Phys., 2016, 18, 28939
    DOI: 10.1039/C6CP03426H

Search articles by author

Spotlight

Advertisements