7wlt: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==the Curved Structure of mPIEZO1 in Lipid Bilayer== | ==the Curved Structure of mPIEZO1 in Lipid Bilayer== | ||
<StructureSection load='7wlt' size='340' side='right'caption='[[7wlt]]' scene=''> | <StructureSection load='7wlt' size='340' side='right'caption='[[7wlt]], [[Resolution|resolution]] 3.46Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WLT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WLT FirstGlance]. <br> | <table><tr><td colspan='2'>[[7wlt]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WLT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WLT FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wlt OCA], [https://pdbe.org/7wlt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wlt RCSB], [https://www.ebi.ac.uk/pdbsum/7wlt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wlt ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=PLX:(9R,11S)-9-({[(1S)-1-HYDROXYHEXADECYL]OXY}METHYL)-2,2-DIMETHYL-5,7,10-TRIOXA-2LAMBDA~5~-AZA-6LAMBDA~5~-PHOSPHAOCTACOSANE-6,6,11-TRIOL'>PLX</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wlt OCA], [https://pdbe.org/7wlt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wlt RCSB], [https://www.ebi.ac.uk/pdbsum/7wlt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wlt ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/PIEZ1_MOUSE 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.<ref>PMID:20813920</ref> <ref>PMID:22343900</ref> <ref>PMID:24157948</ref> <ref>PMID:24958852</ref> <ref>PMID:25119035</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
PIEZO channels respond to piconewton-scale forces to mediate critical physiological and pathophysiological processes(1-5). Detergent-solubilized PIEZO channels form bowl-shaped trimers comprising a central ion-conducting pore with an extracellular cap and three curved and non-planar blades with intracellular beams(6-10), which may undergo force-induced deformation within lipid membranes(11). However, the structures and mechanisms underlying the gating dynamics of PIEZO channels in lipid membranes remain unresolved. Here we determine the curved and flattened structures of PIEZO1 reconstituted in liposome vesicles, directly visualizing the substantial deformability of the PIEZO1-lipid bilayer system and an in-plane areal expansion of approximately 300 nm(2) in the flattened structure. The curved structure of PIEZO1 resembles the structure determined from detergent micelles, but has numerous bound phospholipids. By contrast, the flattened structure exhibits membrane tension-induced flattening of the blade, bending of the beam and detaching and rotating of the cap, which could collectively lead to gating of the ion-conducting pathway. On the basis of the measured in-plane membrane area expansion and stiffness constant of PIEZO1 (ref. (11)), we calculate a half maximal activation tension of about 1.9 pN nm(-1), matching experimentally measured values. Thus, our studies provide a fundamental understanding of how the notable deformability and structural rearrangement of PIEZO1 achieve exquisite mechanosensitivity and unique curvature-based gating in lipid membranes. | |||
Structure deformation and curvature sensing of PIEZO1 in lipid membranes.,Yang X, Lin C, Chen X, Li S, Li X, Xiao B Nature. 2022 Apr;604(7905):377-383. doi: 10.1038/s41586-022-04574-8. Epub 2022, Apr 6. PMID:35388220<ref>PMID:35388220</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7wlt" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chen X]] | [[Category: Chen, X]] | ||
[[Category: Li S]] | [[Category: Li, S]] | ||
[[Category: Lin C]] | [[Category: Lin, C]] | ||
[[Category: Yang X]] | [[Category: Yang, X]] | ||
[[Category: Complex]] | |||
[[Category: Flexible]] | |||
[[Category: Force]] | |||
[[Category: Membrane protein]] | |||
Revision as of 06:13, 21 April 2022
the Curved Structure of mPIEZO1 in Lipid Bilayerthe Curved Structure of mPIEZO1 in Lipid Bilayer
Structural highlights
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 PubMedPIEZO channels respond to piconewton-scale forces to mediate critical physiological and pathophysiological processes(1-5). Detergent-solubilized PIEZO channels form bowl-shaped trimers comprising a central ion-conducting pore with an extracellular cap and three curved and non-planar blades with intracellular beams(6-10), which may undergo force-induced deformation within lipid membranes(11). However, the structures and mechanisms underlying the gating dynamics of PIEZO channels in lipid membranes remain unresolved. Here we determine the curved and flattened structures of PIEZO1 reconstituted in liposome vesicles, directly visualizing the substantial deformability of the PIEZO1-lipid bilayer system and an in-plane areal expansion of approximately 300 nm(2) in the flattened structure. The curved structure of PIEZO1 resembles the structure determined from detergent micelles, but has numerous bound phospholipids. By contrast, the flattened structure exhibits membrane tension-induced flattening of the blade, bending of the beam and detaching and rotating of the cap, which could collectively lead to gating of the ion-conducting pathway. On the basis of the measured in-plane membrane area expansion and stiffness constant of PIEZO1 (ref. (11)), we calculate a half maximal activation tension of about 1.9 pN nm(-1), matching experimentally measured values. Thus, our studies provide a fundamental understanding of how the notable deformability and structural rearrangement of PIEZO1 achieve exquisite mechanosensitivity and unique curvature-based gating in lipid membranes. Structure deformation and curvature sensing of PIEZO1 in lipid membranes.,Yang X, Lin C, Chen X, Li S, Li X, Xiao B Nature. 2022 Apr;604(7905):377-383. doi: 10.1038/s41586-022-04574-8. Epub 2022, Apr 6. PMID:35388220[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||