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Tytuł pozycji:

A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel.

Tytuł:
A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel.
Autorzy:
Geng J; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Liu W; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Joint Graduate Program of Peking-Tsinghua-NIBS, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Zhou H; MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Zhang T; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Wang L; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Zhang M; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Li Y; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Shen B; MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Li X; MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: .
Xiao B; State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China. Electronic address: .
Źródło:
Neuron [Neuron] 2020 May 06; Vol. 106 (3), pp. 438-451.e6. Date of Electronic Publication: 2020 Mar 05.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: [Cambridge, Mass. : Cell Press, c1988-
MeSH Terms:
Ion Channel Gating*
Ion Channels/*metabolism
Animals ; HEK293 Cells ; HeLa Cells ; Humans ; Ion Channels/chemistry ; Male ; Mechanotransduction, Cellular ; Mice ; Mice, Inbred C57BL ; Protein Isoforms/chemistry ; Protein Isoforms/metabolism
Contributed Indexing:
Keywords: Piezo1; Piezo2; gating; ion permeation; isoform; mechanosensitive ion channel; mechanotransduction; plug-and-latch
Substance Nomenclature:
0 (Ion Channels)
0 (PIEZO1 protein, human)
0 (PIEZO2 protein, human)
0 (Protein Isoforms)
Entry Date(s):
Date Created: 20200307 Date Completed: 20200824 Latest Revision: 20200824
Update Code:
20240105
DOI:
10.1016/j.neuron.2020.02.010
PMID:
32142647
Czasopismo naukowe
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.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Comment in: Neuron. 2020 May 6;106(3):361-363. (PMID: 32380048)

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