6pvt

Publication Abstract from PubMed

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-A solid-state NMR structures of the transmembrane domain of the closed and open BM2 channels in a phospholipid environment. Upon activation, the transmembrane helices increase the tilt angle by 6 degrees and the average pore diameter enlarges by 2.1 A. 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 side chain dynamics are the essential driver of proton shuttling.

Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism.,Mandala VS, Loftis AR, Shcherbakov AA, Pentelute BL, Hong M Nat Struct Mol Biol. 2020 Feb;27(2):160-167. doi: 10.1038/s41594-019-0371-2. Epub, 2020 Feb 3. PMID:32015551^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.