2kj1 Citations

Solution structure and functional analysis of the influenza B proton channel.

OpenAccess logo Nat Struct Mol Biol 16 1267-71 (2009)
Cited: 81 times
EuropePMC logo PMID: 19898475

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 degrees 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.

Reviews - 2kj1 mentioned but not cited (2)

  1. Influenza M2 proton channels. Pielak RM, Chou JJ. Biochim Biophys Acta 1808 522-529 (2011)
  2. Mechanism of function of viral channel proteins and implications for drug development. Fischer WB, Wang YT, Schindler C, Chen CP. Int Rev Cell Mol Biol 294 259-321 (2012)

Articles - 2kj1 mentioned but not cited (2)



Reviews citing this publication (23)

  1. Structural and dynamic mechanisms for the function and inhibition of the M2 proton channel from influenza A virus. Wang J, Qiu JX, Soto C, DeGrado WF. Curr Opin Struct Biol 21 68-80 (2011)
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  6. Characterization of the SARS-CoV-2 E Protein: Sequence, Structure, Viroporin, and Inhibitors. Cao Y, Yang R, Lee I, Zhang W, Sun J, Wang W, Meng X. Protein Sci 30 1114-1130 (2021)
  7. Flu channel drug resistance: a tale of two sites. Pielak RM, Chou JJ. Protein Cell 1 246-258 (2010)
  8. Influenza A Virus Nucleoprotein: A Highly Conserved Multi-Functional Viral Protein as a Hot Antiviral Drug Target. Hu Y, Sneyd H, Dekant R, Wang J. Curr Top Med Chem 17 2271-2285 (2017)
  9. Influenza viruses - antiviral therapy and resistance. Duwe S. GMS Infect Dis 5 Doc04 (2017)
  10. Modeling the membrane environment has implications for membrane protein structure and function: influenza A M2 protein. Zhou HX, Cross TA. Protein Sci 22 381-394 (2013)
  11. Applications of NMR to membrane proteins. Opella SJ, Marassi FM. Arch Biochem Biophys 628 92-101 (2017)
  12. The minimalist architectures of viroporins and their therapeutic implications. OuYang B, Chou JJ. Biochim Biophys Acta 1838 1058-1067 (2014)
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  15. Viroporins in the Influenza Virus. To J, Torres J. Cells 8 E654 (2019)
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  17. The present and future of solution NMR in investigating the structure and dynamics of channels and transporters. Oxenoid K, Chou JJ. Curr Opin Struct Biol 23 547-554 (2013)
  18. Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. Sharma M, Li C, Busath DD, Zhou HX, Cross TA. Biochim Biophys Acta 1808 538-546 (2011)
  19. NMR structures of polytopic integral membrane proteins. Patching SG. Mol Membr Biol 28 370-397 (2011)
  20. The Structure, Function, and Pathobiology of the Influenza A and B Virus Ion Channels. Lamb RA. Cold Spring Harb Perspect Med 10 a038505 (2020)
  21. Prophylaxis and treatment of influenza: options, antiviral susceptibility, and existing recommendations. Duwe SC, Schmidt B, Gärtner BC, Timm J, Adams O, Fickenscher H, Schmidtke M. GMS Infect Dis 9 Doc02 (2021)
  22. Natural History of Influenza B Virus-Current Knowledge on Treatment, Resistance and Therapeutic Options. Din GU, Hasham K, Amjad MN, Hu Y. Curr Issues Mol Biol 46 183-199 (2023)
  23. Viral channel forming proteins--How to assemble and depolarize lipid membranes in silico. Fischer WB, Kalita MM, Heermann D. Biochim Biophys Acta 1858 1710-1721 (2016)

Articles citing this publication (54)