Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel

Pervushin, Konstantin; Tan, Edward; Parthasarathy, Krupakar; Lin, Xin; Jiang, Feng Li; Yu, Dejie; Vararattanavech, Ardcharaporn; Soong, Tuck Wah; Liu, Ding Xiang; Torres, Jaume

Another important issue is the effect of the extramembrane domain on channel function and stability. For example, in M2 proton channel from influenza A, truncating the cytoplasmic tail alters ion channel activity when M2 is expressed in oocytes of Xenopus laevis [50] , and analytical ultracentrifugation showed that the full-length protein stabilizes the M2 tetramer by Notice the significant large inward and outward currents recorded from SARS-CoV E protein, in contrast to vector alone and untransfected HEK-293 cell controls (*, two-tail unpaired T test, p,0.05, compared to vector control group). (C) HMA (10 mM) significantly reduced the whole cell current through SARS-CoV E protein (*, two-tail unpaired T test, p,0.05, compared to control). (D) same plot for amiloride (10 mM) , where the small difference with the control was not found to be statistically significant (see text). doi:10.1371/journal.ppat.1000511.g007 approximately 7 kcal/mol [51] . In SARS-CoV E, preliminary sedimentation equilibrium experiments (unpublished data) suggest a slightly lower association constant in a monomer-pentamer equilibrium for full length SARS-CoV E protein, or for a synthetic ETM spanning residues 7-42 (K a ,10 15 ), when compared to ETM (K a ,10 17 ) [38] . Thus, the extramembrane residues may be slightly destabilizing for the SARS-CoV E pentamer.