Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis
Figure 6
Spatial distribution of the mutations obtained in rSARS-CoV-EIC− after serial infections.
(A) Left diagram represents a top view of E protein transmembrane domain and the spatial distribution of the amino acids within the alpha helix. Blue and red circles correspond to amino acids N15 and V25, respectively, originally mutated to inhibit IC activity. Yellow circles surround the amino acids that changed after evolution of V25F mutant. Arrow at position 15 points the lumen of the ion channel pore. Right graphic depicts the pentamer conformation of E protein that forms the ion conductive pore and the positions of both the mutated residue at position 25 and the evolved mutations at positions 19, 25, 26, 27, 30 and 37. Evolved changes map close to the originally mutated residue in the monomer-monomer interface. (B) Pentameric model of SARS-CoV E protein from a lateral (left) or a top view (right). This model was first proposed from linear dichroism of isotopically labeled E protein transmembrane peptides in lipid bilayers [29], [32]. The residues involved in ion channel inhibition (N15 in blue and V25 in red) or mutated after viral evolution (L19, F26, L27, T30 and L37 in yellow) are highlighted.