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Mechanism of influenza A M2 transmembrane domain assembly in lipid membranes
M2 from influenza A virus functions as an oligomeric proton channel essential for the viral cycle, hence it is a high-priority pharmacological target whose structure and functions require better understanding. We studied the mechanism of M2 transmembrane domain (M2TMD) assembly in lipid membranes by...
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Published in: | Scientific reports 2015-07, Vol.5 (1), p.11757-11757, Article 11757 |
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description | M2 from influenza A virus functions as an oligomeric proton channel essential for the viral cycle, hence it is a high-priority pharmacological target whose structure and functions require better understanding. We studied the mechanism of M2 transmembrane domain (M2TMD) assembly in lipid membranes by the powerful biophysical technique of double electron-electron resonance (DEER) spectroscopy. By varying the M2TMD-to-lipid molar ratio over a wide range from 1:18,800 to 1:160, we found that M2TMD exists as monomers, dimers, and tetramers whose relative populations shift to tetramers with the increase of peptide-to-lipid (P/L) molar ratio. Our results strongly support the tandem mechanism of M2 assembly that is monomers-to-dimer then dimers-to-tetramer, since tight dimers are abundant at small P/L's, and thereafter they assemble as dimers of dimers in weaker tetramers. The stepwise mechanism found for a single-pass membrane protein oligomeric assembly should contribute to the knowledge of the association steps in membrane protein folding. |
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The stepwise mechanism found for a single-pass membrane protein oligomeric assembly should contribute to the knowledge of the association steps in membrane protein folding.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>26190831</pmid><doi>10.1038/srep11757</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Cell Membrane - metabolism Humans Hydrogen-Ion Concentration Influenza Influenza A Influenza A virus - metabolism Lipid Bilayers - metabolism Lipid membranes Lipids Membrane Lipids - metabolism Membrane proteins Monomers Peptides - metabolism Protein folding Protein Interaction Domains and Motifs Protein Multimerization Spectroscopy Transmembrane domains Viral Matrix Proteins - chemistry Viral Matrix Proteins - metabolism |
title | Mechanism of influenza A M2 transmembrane domain assembly in lipid membranes |
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