5z10

From Proteopedia

(Difference between revisions)

Current revision

Structure of the mechanosensitive Piezo1 channel

5z10, resolution 3.97Å

Structural highlights

5z10 is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Piezo1, Fam38a (LK3 transgenic mice)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PIEZ1_MOUSE] Pore-forming subunit of a mechanosensitive non-specific cation channel. Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling. In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation. Plays a key role in blood vessel formation and vascular structure in both development and adult physiology.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The mechanosensitive Piezo channels function as key eukaryotic mechanotransducers. However, their structures and mechanogating mechanisms remain unknown. Here we determine the three-bladed, propeller-like electron cryo-microscopy structure of mouse Piezo1 and functionally reveal its mechanotransduction components. Despite the lack of sequence repetition, we identify nine repetitive units consisting of four transmembrane helices each-which we term transmembrane helical units (THUs)-which assemble into a highly curved blade-like structure. The last transmembrane helix encloses a hydrophobic pore, followed by three intracellular fenestration sites and side portals that contain pore-property-determining residues. The central region forms a 90 A-long intracellular beam-like structure, which undergoes a lever-like motion to connect THUs to the pore via the interfaces of the C-terminal domain, the anchor-resembling domain and the outer helix. Deleting extracellular loops in the distal THUs or mutating single residues in the beam impairs the mechanical activation of Piezo1. Overall, Piezo1 possesses a unique 38-transmembrane-helix topology and designated mechanotransduction components, which enable a lever-like mechanogating mechanism.

Structure and mechanogating mechanism of the Piezo1 channel.,Zhao Q, Zhou H, Chi S, Wang Y, Wang J, Geng J, Wu K, Liu W, Zhang T, Dong MQ, Wang J, Li X, Xiao B Nature. 2018 Feb 22;554(7693):487-492. doi: 10.1038/nature25743. Epub 2018 Jan, 22. PMID:29469092^[6]

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

References

↑ Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010 Oct 1;330(6000):55-60. doi: 10.1126/science.1193270. Epub 2010 Sep , 2. PMID:20813920 doi:http://dx.doi.org/10.1126/science.1193270
↑ Coste B, Xiao B, Santos JS, Syeda R, Grandl J, Spencer KS, Kim SE, Schmidt M, Mathur J, Dubin AE, Montal M, Patapoutian A. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature. 2012 Feb 19;483(7388):176-81. doi: 10.1038/nature10812. PMID:22343900 doi:http://dx.doi.org/10.1038/nature10812
↑ Peyronnet R, Martins JR, Duprat F, Demolombe S, Arhatte M, Jodar M, Tauc M, Duranton C, Paulais M, Teulon J, Honore E, Patel A. Piezo1-dependent stretch-activated channels are inhibited by Polycystin-2 in renal tubular epithelial cells. EMBO Rep. 2013 Dec;14(12):1143-8. doi: 10.1038/embor.2013.170. Epub 2013 Oct 25. PMID:24157948 doi:http://dx.doi.org/10.1038/embor.2013.170
↑ Ranade SS, Qiu Z, Woo SH, Hur SS, Murthy SE, Cahalan SM, Xu J, Mathur J, Bandell M, Coste B, Li YS, Chien S, Patapoutian A. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10347-52. doi:, 10.1073/pnas.1409233111. Epub 2014 Jun 23. PMID:24958852 doi:http://dx.doi.org/10.1073/pnas.1409233111
↑ Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ, Sedo A, Hyman AJ, McKeown L, Young RS, Yuldasheva NY, Majeed Y, Wilson LA, Rode B, Bailey MA, Kim HR, Fu Z, Carter DA, Bilton J, Imrie H, Ajuh P, Dear TN, Cubbon RM, Kearney MT, Prasad KR, Evans PC, Ainscough JF, Beech DJ. Piezo1 integration of vascular architecture with physiological force. Nature. 2014 Nov 13;515(7526):279-82. doi: 10.1038/nature13701. Epub 2014 Aug 10. PMID:25119035 doi:http://dx.doi.org/10.1038/nature13701
↑ Zhao Q, Zhou H, Chi S, Wang Y, Wang J, Geng J, Wu K, Liu W, Zhang T, Dong MQ, Wang J, Li X, Xiao B. Structure and mechanogating mechanism of the Piezo1 channel. Nature. 2018 Feb 22;554(7693):487-492. doi: 10.1038/nature25743. Epub 2018 Jan, 22. PMID:29469092 doi:http://dx.doi.org/10.1038/nature25743

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5z10"

@@ Line 3: / Line 3: @@
 <SX load='5z10' size='340' side='right' viewer='molstar' caption='[[5z10]], [[Resolution|resolution]] 3.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5z10]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z10 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5z10]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z10 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Z10 FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Piezo1, Fam38a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5z10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z10 OCA], [http://pdbe.org/5z10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z10 RCSB], [http://www.ebi.ac.uk/pdbsum/5z10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z10 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5z10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z10 OCA], [http://pdbe.org/5z10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z10 RCSB], [http://www.ebi.ac.uk/pdbsum/5z10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z10 ProSAT]</span></td></tr>
 </table>
 == Function ==

5z10

From Proteopedia

Current revision

Structure of the mechanosensitive Piezo1 channel

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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