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The conformation of the pore region of the M2 proton channel depends on lipid bilayer environment
Author(s) -
DuongLy Krisna C.,
Nanda Vikas,
DeGrado William F.,
Howard Kathleen P.
Publication year - 2005
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 - 10.1110/ps.041185805
Subject(s) - tetramer , lipid bilayer , chemistry , biophysics , bilayer , transmembrane domain , transmembrane protein , nitroxide mediated radical polymerization , crystallography , protein structure , conformational change , helix (gastropod) , stereochemistry , membrane , biochemistry , biology , monomer , receptor , radical polymerization , organic chemistry , enzyme , polymer , ecology , snail
The M2 protein from influenza A virus is a 97‐amino‐acid protein with a single transmembrane helix that forms proton‐selective channels essential to virus function. The hydrophobic transmembrane domain of the M2 protein (M2TM) contains a sequence motif that mediates the formation of functional tetramers in membrane environments. A variety of structural models have previously been proposed which differ in the degree of helix tilt, with proposed tilts ranging from ∼15° to 38°. An important issue for understanding the structure of M2TM is the role of peptide–lipid interactions in the stabilization of the lipid bilayer bound tetramer. Here, we labeled the N terminus of M2TM with a nitroxide and studied the tetramer reconstituted into lipid bilayers of different thicknesses using EPR spectroscopy. Analyses of spectral changes provide evidence that the lipid bilayer does influence the conformation. The structural plasticity displayed by M2TM in response to membrane composition may be indicative of functional requirements for conformational change. The various structural models for M2TM proposed to date—each defined by a different set of criteria and in a different environment—might provide snapshots of the distinct conformational states sampled by the protein.