tetano
Editor, Senior Moderator
Nat Struct Mol Biol. 2020 Feb 3. doi: 10.1038/s41594-019-0371-2. [Epub ahead of print] [h=1]Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism.[/h]
Mandala VS[SUP]1[/SUP], Loftis AR[SUP]1[/SUP], Shcherbakov AA[SUP]1[/SUP], Pentelute BL[SUP]1[/SUP], Hong M[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-? 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? and the average pore diameter enlarges by 2.1 ?. 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.
PMID: 32015551 DOI: 10.1038/s41594-019-0371-2
Mandala VS[SUP]1[/SUP], Loftis AR[SUP]1[/SUP], Shcherbakov AA[SUP]1[/SUP], Pentelute BL[SUP]1[/SUP], Hong M[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-? 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? and the average pore diameter enlarges by 2.1 ?. 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.
PMID: 32015551 DOI: 10.1038/s41594-019-0371-2