Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Structure
2013 Nov 05;2111:2033-41. doi: 10.1016/j.str.2013.08.029.
Show Gene links
Show Anatomy links
Asp44 stabilizes the Trp41 gate of the M2 proton channel of influenza A virus.
Ma C, Fiorin G, Carnevale V, Wang J, Lamb RA, Klein ML, Wu Y, Pinto LH, DeGrado WF.
???displayArticle.abstract???
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.
Acharya,
Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus.
2010, Pubmed,
Xenbase
Acharya,
Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus.
2010,
Pubmed
,
Xenbase Balannik,
Functional studies and modeling of pore-lining residue mutants of the influenza a virus M2 ion channel.
2010,
Pubmed
,
Xenbase Betakova,
Influence of residue 44 on the activity of the M2 proton channel of influenza A virus.
2005,
Pubmed Cady,
Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers.
2010,
Pubmed Cady,
Structure of amantadine-bound M2 transmembrane peptide of influenza A in lipid bilayers from magic-angle-spinning solid-state NMR: the role of Ser31 in amantadine binding.
2009,
Pubmed Chizhmakov,
Differences in conductance of M2 proton channels of two influenza viruses at low and high pH.
2003,
Pubmed Delaglio,
NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
1995,
Pubmed Grambas,
Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses.
1992,
Pubmed Hong,
Structural basis for proton conduction and inhibition by the influenza M2 protein.
2012,
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 Hu,
Mechanisms of proton conduction and gating in influenza M2 proton channels from solid-state NMR.
2010,
Pubmed Humphrey,
VMD: visual molecular dynamics.
1996,
Pubmed Khurana,
Molecular dynamics calculations suggest a conduction mechanism for the M2 proton channel from influenza A virus.
2009,
Pubmed MacKerell,
Development and current status of the CHARMM force field for nucleic acids.
,
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 Nguyen,
pH-induced conformational change of the influenza M2 protein C-terminal domain.
2008,
Pubmed
,
Xenbase Phillips,
Scalable molecular dynamics with NAMD.
2005,
Pubmed Pielak,
Kinetic analysis of the M2 proton conduction of the influenza virus.
2010,
Pubmed Pinto,
Influenza virus proton channels.
2006,
Pubmed Pinto,
A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity.
1997,
Pubmed
,
Xenbase Schnell,
Structure and mechanism of the M2 proton channel of influenza A virus.
2008,
Pubmed Sharma,
Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer.
2010,
Pubmed Stouffer,
Structural basis for the function and inhibition of an influenza virus proton channel.
2008,
Pubmed Tang,
The gate of the influenza virus M2 proton channel is formed by a single tryptophan residue.
2002,
Pubmed
,
Xenbase Thomaston,
Detection of drug-induced conformational change of a transmembrane protein in lipid bilayers using site-directed spin labeling.
2013,
Pubmed Zhou,
A theory for the proton transport of the influenza virus M2 protein: extensive test against conductance data.
2011,
Pubmed
