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Solution structure and functional analysis of the influenza B proton channel

Nature Structural & Molecular Biology volume 16, pages 1267–1271 (2009)Cite this article

Abstract

Influenza B virus contains an integral membrane protein, BM2, that oligomerizes in the viral membrane to form a pH-activated proton channel. Here we report the solution structures of both the membrane-embedded channel domain and the cytoplasmic domain of BM2. The channel domain assumes a left-handed coiled-coil tetramer formation with a helical packing angle of −37° to form a polar pore in the membrane for conducting ions. Mutagenesis and proton flux experiments identified residues involved in proton relay and suggest a mechanism of proton conductance. The cytoplasmic domain of BM2 also forms a coiled-coil tetramer. It has a bipolar charge distribution, in which a negatively charged region interacts specifically with the M1 matrix protein that is involved in packaging the genome in the virion. This interaction suggests BM2 also recruits matrix proteins to the cell surface during virus budding, making BM2 an unusual membrane protein with the dual roles of conducting ions and recruiting proteins to the membrane.

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Figure 1: Solution structure of BM2 from influenza B virus.
Figure 2: Assembly of the H+ conducting pore.
Figure 3: Interaction between BM2 cytoplasmic domain and BM1 matrix protein.
Figure 4: The dual functionality of BM2.

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Acknowledgements

We thank M. Berardi for insightful discussion on the interaction between BM2 and M1 matrix protein. This work was supported by grants from the US National Institutes of Health (AI054520 to J.J.C.) and the Pew Scholars Program in Biomedical Sciences to J.J.C.

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Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA

    Junfeng Wang, Rafal M Pielak, Mark A McClintock & James J Chou

  2. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA

    Rafal M Pielak

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  1. Junfeng Wang
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  2. Rafal M Pielak
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  3. Mark A McClintock
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  4. James J Chou
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Contributions

J.W. and J.J.C. determined the BM2 structures; R.M.P. performed proton conductance assays; J.W. and M.A.M. performed the BM2-BM1 interaction experiment; J.J.C., R.M.P. and J.W. wrote the paper; J.J.C. supervised the research.

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Correspondence to James J Chou.

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Wang, J., Pielak, R., McClintock, M. et al. Solution structure and functional analysis of the influenza B proton channel. Nat Struct Mol Biol 16, 1267–1271 (2009). https://doi.org/10.1038/nsmb.1707

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