The influenza B virus BM2
protein contains 109
amino acid residues and it is translated from a bicistronic
mRNA in an open reading frame that is +2
nucleotides with respect to the matrix (M1)
protein. The amino acid sequence of BM2 contains a hydrophobic region (residues 7-25) that could act as a transmembrane (TM) anchor. Analysis of properties of the BM2
protein, including
detergent solubility, insolubility in
alkali pH 11, flotation in membrane fractions, and
epitope-tagging immunocytochemistry, indicates BM2
protein is the fourth
integral membrane protein encoded by influenza B virus in addition to
hemagglutinin (HA),
neuraminidase (NA), and the NB
glycoprotein. Biochemical analysis indicates that the BM2
protein adopts an N(out)C(in) orientation in membranes and fluorescence microscopy indicates BM2 is expressed at the cell surface. As the BM2
protein possesses only a single hydrophobic domain and lacks a cleavable
signal sequence, it is another example of a Type III
integral membrane protein, in addition to M(2), NB, and CM2
proteins of
influenza A, B, and C viruses, respectively. Chemical cross-linking studies indicate that the BM2
protein is oligomeric, most likely a tetramer. Comparison of the amino acid sequence of the TM domain of the BM2
protein with the sequence of the TM domain of the
proton-selective
ion channel M(2)
protein of influenza A virus is intriguing as M(2)
protein residues critical for ion selectivity/activation and channel gating (H(37) and W(41), respectively) are found at the same relative position and spacing in the BM2
protein (H(19) and W(23)).