title: Modeling the membrane environment has implications for membrane protein structure and function: influenza A M2 protein.
abstract: The M2 protein, a proton channel, from Influenza A has been structurally characterized by X-ray diffraction and by solution and solid-state NMR spectroscopy in a variety of membrane mimetic environments. These structures show substantial backbone differences even though they all present a left-handed tetrameric helical bundle for the transmembrane domain. Variations in the helix tilt influence drug binding and the chemistry of the histidine tetrad responsible for acid activation, proton selectivity and transport. Some of the major structural differences do not arise from the lack of precision, but instead can be traced to the influences of the membrane mimetic environments. The structure in lipid bilayers displays unique chemistry for the histidine tetrad, which binds two protons cooperatively to form a pair of imidazole-imidazolium dimers. The resulting interhistidine hydrogen bonds contribute to a three orders of magnitude enhancement in tetramer stability. Integration with computation has provided detailed understanding of the functional mechanism for proton selectivity, conductance and gating of this important drug target.
authors: Department of Physics, Florida State University, Tallahassee, Florida 32306, USA.
authors: Huan-Xiang
authors: HX
authors: Zhou
authors: Timothy A
authors: TA
authors: Cross
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D024882:Drug Resistance, Viral; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D000596:Amino Acids; D008565:Membrane Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
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