Solution structure and functional analysis of the influenza B proton channel

• Published in: Nature structural & molecular biology Vol. 16; no. 12; pp. 1267 - 1271
• Main Authors: McClintock, Mark A, Wang, Junfeng, Chou, James J, Pielak, Rafal M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2009; Nature Publishing Group
• Subjects: Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Genetic aspects; Health aspects; Influenza; Influenza B virus; Influenza B virus - chemistry; Influenza viruses; Ion channels; Ions; Life Sciences; Membrane Biology; Membrane proteins; Membranes; Models, Biological; Models, Molecular; Molecular biology; Molecular structure; Mutagenesis, Site-Directed; Nuclear Magnetic Resonance, Biomolecular; Packaging; Physiological aspects; Protein Multimerization; Protein Structure; Protein Structure, Quaternary; Proteins; Protons; Structure; Viral Matrix Proteins - metabolism; Viral Proteins - chemistry; Viral Proteins - metabolism; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.1707

Influenza B virus is responsible for about half of all the seasonal flu cases. The integral protein BM2 oligomerizes and forms a pH-activated proton channel that is essential for viral entry into host cells. The solution structures of the membrane-embedded chain domain and the C-terminal cytoplasmic domain reveal significant differences from the AM2 protein of influenza A virus and explain antiviral drug resistance. 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.