Solution structure and functional analysis of the influenza B proton channel

Abstract

Influenza B virus contains an integral membrane protein, BM2, that oligomerizes in the viral membrane to form 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 forms a left-handed coiled-coil tetramer with a helical packing angle of -37{degree sign} 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 another role of BM2 in recruiting the matrix proteins to the cell surface during virus budding. Therefore BM2 is an unusual membrane protein which has the dual functionality of conducting ions and recruiting proteins to the membrane.