Abstract:
:When influenza A virus infects host cells, its integral matrix protein M2 forms a proton-selective channel in the viral envelope. Although X-ray crystallography and NMR studies using fragment peptides have suggested that M2 stably forms a tetrameric channel irrespective of pH, the oligomeric states of the full-length protein in the living cells have not yet been assessed directly. In the present study, we utilized recently developed stoichiometric analytical methods based on fluorescence resonance energy transfer using coiled-coil labeling technique and spectral imaging, and we examined the relationship between the oligomeric states of full-length M2 and its channel activities in living cells. In contrast to previous models, M2 formed proton-conducting dimers at neutral pH and these dimers were converted to tetramers at acidic pH. The antiviral drug amantadine hydrochloride inhibited both tetramerization and channel activity. The removal of cholesterol resulted in a significant decrease in the activity of the dimer. These results indicate that the minimum functional unit of the M2 protein is a dimer, which forms a complex with cholesterol for its function.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Kawano K,Yano Y,Matsuzaki Kdoi
10.1016/j.jmb.2014.05.002subject
Has Abstractpub_date
2014-07-15 00:00:00pages
2679-91issue
14eissn
0022-2836issn
1089-8638pii
S0022-2836(14)00229-0journal_volume
426pub_type
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