Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism.

Abstract

The influenza B M2 (BM2) proton channel is activated by acidic pH to mediate virus uncoating. Unlike influenza A M2 (AM2), which conducts protons with strong inward rectification, BM2 conducts protons both inward and outward. Here we report 1.4- and 1.5-angstrom solid-state NMR structures of the transmembrane domain of the closed and open BM2 channels in phospholipid environment. Upon activation, the transmembrane helices increase the tilt angle by 6˚ and the average pore diameter enlarges by 2.1 Å. BM2 thus undergoes a scissor motion for activation, which differs from the alternating-access motion of AM2. These results indicate that asymmetric proton conduction requires a backbone hinge motion whereas bidirectional conduction is achieved by a symmetric scissor motion. The proton-selective histidine and gating tryptophan in the open BM2 reorient on the microsecond timescale, similar to AM2, indicating that sidechain dynamics are the essential driver of proton shuttling.