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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Bibliographic Details
Published in:Scientific reports 2015-07, Vol.5 (1), p.11757-11757, Article 11757
Main Authors: Georgieva, Elka R., Borbat, Peter P., Norman, Haley D., Freed, Jack H.
Format: Article
Language:English
Subjects:
631/57/2271
631/92/269
Cell Membrane - metabolism
Humanities and Social Sciences
Humans
Hydrogen-Ion Concentration
Influenza
Influenza A
Influenza A virus - metabolism
Lipid Bilayers - metabolism
Lipid membranes
Lipids
Membrane Lipids - metabolism
Membrane proteins
Membranes
Monomers
multidisciplinary
Peptides - metabolism
Protein folding
Protein Interaction Domains and Motifs
Protein Multimerization
Science
Spectroscopy
Transmembrane domains
Viral Matrix Proteins - chemistry
Viral Matrix Proteins - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep11757