Activation of the Influenza B M2 Proton Channel (BM2)

Zhi Yue1, Jiangbo Wu1, Da Teng1

  • 1Department of Chemistry, Chicago Center for Theoretical Chemistry, James Frank Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois 60637, United States.

Biochemistry
|November 3, 2024
PubMed

Insights

Influenza B virus M2 channel (BM2) proton transport mechanisms were simulated. Researchers found His27 influences BM2 activation pH and identified key hydration sites for proton conduction, aiding antiviral drug design.

Area of Science:

  • Biophysics
  • Virology
  • Structural Biology

Background:

  • Influenza B viruses cause significant morbidity and mortality.
  • The influenza B M2 proton channel (BM2) is crucial for viral replication.
  • BM2's proton conductance mechanisms and the role of His27 are not fully understood.

Purpose of the Study:

  • To investigate the pH-dependent conformational switch of wildtype BM2 and an H27A mutant.
  • To elucidate the atomic-level mechanisms of symmetric proton conduction in BM2.

Main Methods:

  • Membrane-enabled continuous constant-pH molecular dynamics simulations.
  • Simulations were performed on wildtype BM2 and a His27 to Alanine (H27A) mutant channel.

Main Results:

  • BM2 activation occurs upon His19 protonation.
  • Lower activation pH compared to AM2 is due to electrostatic repulsion between His19 and His27.
  • Preactivating channel hydration in the C-terminal portion was identified as crucial for proton conduction.

Conclusions:

  • This study provides an atomic-level understanding of BM2 function.
  • Findings lay the groundwork for reactive modeling of proton transport and antiviral drug design.

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