Structure
Volume 21, Issue 11, 5 November 2013, Pages 2033-2041
Journal home page for Structure

Article
Asp44 Stabilizes the Trp41 Gate of the M2 Proton Channel of Influenza A Virus

https://doi.org/10.1016/j.str.2013.08.029Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Asp44 fine-tunes conduction of M2

  • Asp44 slows down diffusion of protons out of an acidified virus interior

  • Asp44 works in concert with Trp41, which is known to serve as a gating residue

  • MD and NMR show that Asp44 stabilizes the closed configuration of M2’s proton gate

Summary

Channel gating and proton conductance of the influenza A virus M2 channel result from complex pH-dependent interactions involving the pore-lining residues His37, Trp41, and Asp44. Protons diffusing from the outside of the virus protonate His37, which opens the Trp41 gate and allows one or more protons to move into the virus interior. The Trp41 gate gives rise to a strong asymmetry in the conductance, favoring rapid proton flux only when the outside is at acid pH. Here, we show that the proton currents recorded for mutants of Asp44, including D44N found in the A/FPV/Rostock/34 strain, lose this asymmetry. Moreover, NMR and MD simulations show that the mutations induce a conformational change similar to that induced by protonation of His37 at low pH, and decrease the structural stability of the hydrophobic seal associated with the Trp41 gate. Thus, Asp44 is able to determine two important properties of the M2 proton channel.

Cited by (0)

7

These authors contributed equally to this work