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Modeling the membrane environment has implications for membrane protein structure and function: Influenza A M2 protein
Author(s) -
Zhou HuanXiang,
Cross Timothy A.
Publication year - 2013
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2232
Subject(s) - chemistry , tetramer , hydrogen bond , histidine , crystallography , transmembrane domain , membrane protein , protein structure , imidazole , nuclear magnetic resonance spectroscopy , membrane , biophysics , stereochemistry , molecule , biochemistry , amino acid , biology , organic chemistry , enzyme
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.