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The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2(+) and 3(+) with a pK(a) near 6. A 1.65 A resolution X-ray structure of the transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.
Balannik,
Functional studies and modeling of pore-lining residue mutants of the influenza a virus M2 ion channel.
2010, Pubmed,
Xenbase
Balannik,
Functional studies and modeling of pore-lining residue mutants of the influenza a virus M2 ion channel.
2010,
Pubmed
,
Xenbase Cady,
Structure and function of the influenza A M2 proton channel.
2009,
Pubmed Cady,
Amantadine-induced conformational and dynamical changes of the influenza M2 transmembrane proton channel.
2008,
Pubmed Cady,
Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers.
2010,
Pubmed Chakrabarti,
Structural determinants of proton blockage in aquaporins.
2004,
Pubmed Chen,
Proton transport behavior through the influenza A M2 channel: insights from molecular simulation.
2007,
Pubmed Chizhmakov,
Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells.
1996,
Pubmed Cruzan,
Quantifying hydrogen bond cooperativity in water: VRT spectroscopy of the water tetramer.
1996,
Pubmed Decoursey,
Voltage-gated proton channels and other proton transfer pathways.
2003,
Pubmed de Groot,
Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF.
2001,
Pubmed Forrest,
Defining the transmembrane helix of M2 protein from influenza A by molecular dynamics simulations in a lipid bilayer.
1999,
Pubmed Harries,
The channel architecture of aquaporin 0 at a 2.2-A resolution.
2004,
Pubmed Headrick,
Spectral signatures of hydrated proton vibrations in water clusters.
2005,
Pubmed Hu,
Histidines, heart of the hydrogen ion channel from influenza A virus: toward an understanding of conductance and proton selectivity.
2006,
Pubmed Hu,
Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus.
2007,
Pubmed Hummer,
Water conduction through the hydrophobic channel of a carbon nanotube.
2001,
Pubmed Humphrey,
VMD: visual molecular dynamics.
1996,
Pubmed Jing,
Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel.
2008,
Pubmed
,
Xenbase Khurana,
Molecular dynamics calculations suggest a conduction mechanism for the M2 proton channel from influenza A virus.
2009,
Pubmed Li,
Solid-state NMR characterization of conformational plasticity within the transmembrane domain of the influenza A M2 proton channel.
2007,
Pubmed Lin,
Definitive assignment of proton selectivity and attoampere unitary current to the M2 ion channel protein of influenza A virus.
2001,
Pubmed Liu,
Structure of a tetrameric MscL in an expanded intermediate state.
2009,
Pubmed Ma,
Identification of the pore-lining residues of the BM2 ion channel protein of influenza B virus.
2008,
Pubmed
,
Xenbase Ma,
Identification of the functional core of the influenza A virus A/M2 proton-selective ion channel.
2009,
Pubmed
,
Xenbase MacKerell,
All-atom empirical potential for molecular modeling and dynamics studies of proteins.
1998,
Pubmed Mould,
Permeation and activation of the M2 ion channel of influenza A virus.
2000,
Pubmed
,
Xenbase Mould,
Mechanism for proton conduction of the M(2) ion channel of influenza A virus.
2000,
Pubmed
,
Xenbase Okada,
Protonation of histidine and histidine-tryptophan interaction in the activation of the M2 ion channel from influenza a virus.
2001,
Pubmed Phillips,
Scalable molecular dynamics with NAMD.
2005,
Pubmed Pielak,
Mechanism of drug inhibition and drug resistance of influenza A M2 channel.
2009,
Pubmed Pinto,
Influenza virus M2 protein has ion channel activity.
1992,
Pubmed
,
Xenbase Pinto,
A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity.
1997,
Pubmed
,
Xenbase Pinto,
The M2 proton channels of influenza A and B viruses.
2006,
Pubmed Robertson,
Spectroscopic determination of the OH- solvation shell in the OH-.(H2O)n clusters.
2003,
Pubmed Schnell,
Structure and mechanism of the M2 proton channel of influenza A virus.
2008,
Pubmed Shin,
Infrared signature of structures associated with the H+(H2O)n (n = 6 to 27) clusters.
2004,
Pubmed Stouffer,
The interplay of functional tuning, drug resistance, and thermodynamic stability in the evolution of the M2 proton channel from the influenza A virus.
2008,
Pubmed
,
Xenbase Stouffer,
Structural basis for the function and inhibition of an influenza virus proton channel.
2008,
Pubmed Sugrue,
Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel.
1991,
Pubmed Tajkhorshid,
Control of the selectivity of the aquaporin water channel family by global orientational tuning.
2002,
Pubmed Tang,
The gate of the influenza virus M2 proton channel is formed by a single tryptophan residue.
2002,
Pubmed
,
Xenbase Tian,
Initial structural and dynamic characterization of the M2 protein transmembrane and amphipathic helices in lipid bilayers.
2003,
Pubmed Tumpey,
Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus.
2002,
Pubmed Venkataraman,
Chemical rescue of histidine selectivity filter mutants of the M2 ion channel of influenza A virus.
2005,
Pubmed
,
Xenbase Vijayvergiya,
Proton conductance of influenza virus M2 protein in planar lipid bilayers.
2004,
Pubmed Wang,
Activation of the M2 ion channel of influenza virus: a role for the transmembrane domain histidine residue.
1995,
Pubmed
,
Xenbase Witter,
Solid-state 19F NMR spectroscopy reveals that Trp41 participates in the gating mechanism of the M2 proton channel of influenza A virus.
2008,
Pubmed Yi,
Conformational heterogeneity of the M2 proton channel and a structural model for channel activation.
2009,
Pubmed Yifrach,
Energetics of pore opening in a voltage-gated K(+) channel.
2002,
Pubmed
,
Xenbase Zhirnov,
Isolation of matrix protein M1 from influenza viruses by acid-dependent extraction with nonionic detergent.
1992,
Pubmed
