Journal article
The Transmembrane Conformation of the Influenza B Virus M2 Protein in Lipid Bilayers
Scientific reports, Vol.9(1), p.3725
03/06/2019
DOI: 10.1038/s41598-019-40217-1
PMCID: PMC6403292
PMID: 30842530
Abstract
Influenza A and B viruses cause seasonal flu epidemics. The M2 protein of influenza B (BM2) is a membrane-embedded tetrameric proton channel that is essential for the viral lifecycle. BM2 is a functional analog of AM2 but shares only 24% sequence identity for the transmembrane (TM) domain. The structure and function of AM2, which is targeted by two antiviral drugs, have been well characterized. In comparison, much less is known about the structure of BM2 and no drug is so far available to inhibit this protein. Here we use solid-state NMR spectroscopy to investigate the conformation of BM2(1-51) in phospholipid bilayers at high pH, which corresponds to the closed state of the channel. Using 2D and 3D correlation NMR experiments, we resolved and assigned the
C and
N chemical shifts of 29 residues of the TM domain, which yielded backbone (φ, ψ) torsion angles. Residues 6-28 form a well-ordered α-helix, whereas residues 1-5 and 29-35 display chemical shifts that are indicative of random coil or β-sheet conformations. The length of the BM2-TM helix resembles that of AM2-TM, despite their markedly different amino acid sequences. In comparison, large
N chemical shift differences are observed between bilayer-bound BM2 and micelle-bound BM2, indicating that the TM helix conformation and the backbone hydrogen bonding in lipid bilayers differ from the micelle-bound conformation. Moreover, H
chemical shifts of micelle-bound BM2 lack the periodic trend expected for coiled coil helices, which disagree with the presence of a coiled coil structure in micelles. These results establish the basis for determining the full three-dimensional structure of the tetrameric BM2 to elucidate its proton-conduction mechanism.
Details
- Title: Subtitle
- The Transmembrane Conformation of the Influenza B Virus M2 Protein in Lipid Bilayers
- Creators
- Venkata S Mandala - Massachusetts Institute of TechnologyShu-Yu Liao - Massachusetts Institute of TechnologyMartin D Gelenter - Massachusetts Institute of TechnologyMei Hong - Massachusetts Institute of Technology
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.9(1), p.3725
- DOI
- 10.1038/s41598-019-40217-1
- PMID
- 30842530
- PMCID
- PMC6403292
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Grant note
- F31 AI133989 / NIAID NIH HHS
- Language
- English
- Date published
- 03/06/2019
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985112880902771
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