View source for 8zu3


==Human PIEZO1-MDFIC==
<StructureSection load='8zu3' size='340' side='right'caption='[[8zu3]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zu3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZU3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=L9Q:(1S)-2-{[(S)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(OCTADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>L9Q</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=8zu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zu3 OCA], [https://pdbe.org/8zu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zu3 RCSB], [https://www.ebi.ac.uk/pdbsum/8zu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zu3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PIEZ1_HUMAN PIEZ1_HUMAN] PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis;Dehydrated hereditary stomatocytosis;Milroy disease. The disease is caused by variants affecting the gene represented in this entry. All disease-causing mutations characterized so far produce a gain-of-function phenotype, mutated channels exhibiting increased cation transport in erythroid cells, that could be due to slower channel inactivation rate compared to the wild-type protein.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/PIEZ1_HUMAN PIEZ1_HUMAN] Pore-forming subunit of a mechanosensitive non-specific cation Piezo channel (PubMed:23479567, PubMed:23695678, PubMed:25955826). Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents (PubMed:25955826). 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 (PubMed:20016066). Piezo channels are homotrimeric three-blade propeller-shaped structure that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (PubMed:25119035). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (By similarity). Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells. In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007).[UniProtKB:E2JF22][UniProtKB:Q91X60]<ref>PMID:25955826</ref> <ref>PMID:29799007</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Zhang MF]]