Influenza B virus BM2 protein is an oligomeric integral membrane protein expressed at the cell surface

Reay G. Paterson, Makoto Takeda, Yuki Ohigashi, Lawrence H. Pinto, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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 NoutCin 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 M2, 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 M2 protein of influenza A virus is intriguing as M2 protein residues critical for ion selectivity/activation and channel gating (H37 and W41, respectively) are found at the same relative position and spacing in the BM2 protein (H19 and W23).

Original languageEnglish (US)
Pages (from-to)7-17
Number of pages11
JournalVirology
Volume306
Issue number1
DOIs
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Virology

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