A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel

Yanfeng Wang, Shaopeng Chi, Huifang Guo, Guang Li, Li Wang, Qiancheng Zhao, Yu Rao, Liansuo Zu, Wei He and Bailong Xiao ()
Additional contact information
Yanfeng Wang: Tsinghua University
Shaopeng Chi: Tsinghua University
Huifang Guo: Peking Union Medical College
Guang Li: Tsinghua University
Li Wang: Tsinghua University
Qiancheng Zhao: Tsinghua University
Yu Rao: Tsinghua University
Liansuo Zu: Tsinghua University
Wei He: Tsinghua University
Bailong Xiao: Tsinghua University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Piezo1 represents a prototype of eukaryotic mechanotransduction channels. The full-length 2547-residue mouse Piezo1 possesses a unique 38-transmembrane-helix (TM) topology and is organized into a three-bladed, propeller-shaped architecture, comprising a central ion-conducting pore, three peripheral blade-like structures, and three 90-Å-long intracellular beam-resembling structures that bridge the blades to the pore. However, how mechanical force and chemicals activate the gigantic Piezo1 machinery remains elusive. Here we identify a novel set of Piezo1 chemical activators, termed Jedi, which activates Piezo1 through the extracellular side of the blade instead of the C-terminal extracellular domain of the pore, indicating long-range allosteric gating. Remarkably, Jedi-induced activation of Piezo1 requires the key mechanotransduction components, including the two extracellular loops in the distal blade and the two leucine residues in the proximal end of the beam. Thus, Piezo1 employs the peripheral blade-beam-constituted lever-like apparatus as a designated transduction pathway for long-distance mechano- and chemical-gating of the pore.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03570-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03570-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-03570-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().