ArticleThe journal of physical chemistry. B2014
Proton release from the histidine-tetrad in the M2 channel of the influenza A virus.
Article in The journal of physical chemistry. B, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
- The interplay of polarizable water and protein in the activation of the M2 channel.Frontiers in pharmacology · 2025Article
- Fluoride Transport and Inhibition Across CLC Transporters.Handbook of experimental pharmacology · 2024Article
- Molecular origins of asymmetric proton conduction in the influenza M2 channel.Biophysical journal · 2023Article
- Development and application of reverse genetic technology for the influenza virus.Virus genes · 2021Review
- From Acid Activation Mechanisms of Proton Conduction to Design of Inhibitors of the M2 Proton Channel of Influenza A Virus.Frontiers in molecular biosciences · 2021Review
- M2 amphipathic helices facilitate pH-dependent conformational transition in influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations.Sensors (Basel, Switzerland) · 2018Article
- Classical Molecular Dynamics with Mobile Protons.Journal of chemical information and modeling · 2017Article
- Acid activation mechanism of the influenza A M2 proton channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Infrared and fluorescence assessment of the hydration status of the tryptophan gate in the influenza A M2 proton channel.Physical chemistry chemical physics : PCCP · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The activity of the M2 proton channel of the influenza A virus is controlled by pH. The tautomeric state and conformation of His37, a key residue in the M2 transmembrane four-helix bundle, controls the gating of the channel. Previously, we compared the energetics and dynamics of two alternative conformations of the doubly protonated state at neutral pH, namely, a 4-fold symmetric "histidine-box" and a 2-fold symmetric "dimer-of-dimers", and proposed a multiconfiguration model for this charge state. Here, we elaborate this model by further studying configurations of the His37 tetrad in the triply protonated state and its subsequent deprotonation via quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations, starting with the aforementioned configurations, to gain information about proton release in a viral membrane environment. Interestingly, the two configurations converge under acidic pH conditions. Protons can be transferred from one charged His37 to a neighboring water cluster at the C-terminal side of the channel when the Trp41 gate is open transiently. With limited backbone expansion, the free energy barrier for proton release to the viral interior at low pH is ~6.5 kcal/mol in both models, which is much lower than at either neutral pH or for an isolated His37 cluster without a membrane environment. Our calculations also suggest that the M2 protein would seem to exclude the entrance of anions into the central channel through a special mechanism, due to the latter's potential inhibitory effect on proton conduction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.