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TitleA Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel.
Journal, issue, pagesNeuron, Vol. 106, Issue 3, Page 438-451.e6, Year 2020
Publish dateMay 6, 2020
AuthorsJie Geng / Wenhao Liu / Heng Zhou / Tingxin Zhang / Li Wang / Mingmin Zhang / Yiran Li / Bo Shen / Xueming Li / Bailong Xiao /
PubMed AbstractThe mechanosensitive Piezo1 and Piezo2 channels convert mechanical force into cation permeation. However, their precise mechanogating and regulatory mechanisms remain elusive. Here, we report that ...The mechanosensitive Piezo1 and Piezo2 channels convert mechanical force into cation permeation. However, their precise mechanogating and regulatory mechanisms remain elusive. Here, we report that Piezo1 utilizes three lateral ion-conducting portals equipped with physical gates for cooperative gating and splicing regulation. Mutating residues lining the portal converts Piezo1 into an anion-selective channel, demonstrating the portal-based cation-permeating pathway. Intriguingly, the portal is physically blocked with a plug domain, which undergoes alternative splicing in both Piezo1 and Piezo2. The Piezo1 isoform has local openings of the portals, enlarged single-channel conductance and sensitized mechanosensitivity. Remarkably, the three plugs are strategically latched onto the central axis for coordinated gating of the three portals. Disrupting the latching induces three quantal sub-conductance states in Piezo1, but not in the isoform. Together, we propose that Piezo utilizes an elegant plug-and-latch mechanism to physically and coordinately gate the lateral portals through the spliceable plug gates.
External linksNeuron / PubMed:32142647
MethodsEM (single particle)
Resolution4.5 Å
Structure data

0946

6lqi

EMDB-0946, PDB-6lqi:
Cryo-EM structure of the mouse Piezo1 isoform Piezo1.1
Method: EM (single particle) / Resolution: 4.5 Å

Source
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / Piezo1.1 / Mechanogating / Mechanotransduction channel / isoform

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