6d1w: Difference between revisions
New page: '''Unreleased structure''' The entry 6d1w is ON HOLD Authors: Zheng, W., Yang, X., Bulkley, D., Chen, X.Z., Cao, E. Description: human PKD2 F604P mutant [[Category: Unreleased Structur... |
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The | ==human PKD2 F604P mutant== | ||
<SX load='6d1w' size='340' side='right' viewer='molstar' caption='[[6d1w]], [[Resolution|resolution]] 3.54Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6d1w]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D1W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D1W FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKD2, TRPP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6d1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1w OCA], [http://pdbe.org/6d1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d1w RCSB], [http://www.ebi.ac.uk/pdbsum/6d1w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1w ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/PKD2_HUMAN PKD2_HUMAN]] Defects in PKD2 are the cause of polycystic kidney disease 2 (PKD2) [MIM:[http://omim.org/entry/613095 613095]]. PKD2 is a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy.<ref>PMID:9326320</ref> <ref>PMID:10541293</ref> <ref>PMID:10411676</ref> <ref>PMID:10835625</ref> <ref>PMID:11968093</ref> <ref>PMID:12707387</ref> <ref>PMID:14993477</ref> <ref>PMID:15772804</ref> <ref>PMID:21115670</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/PKD2_HUMAN PKD2_HUMAN]] Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis (By similarity). Acts as a regulator of cilium length, together with PKD1 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). Functions as a calcium permeable cation channel. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a single-residue hydrophobic gate in PKD2. We find that a PKD2 gain-of-function gate mutant effectively rescues PKD2 knockdown-induced phenotypes in embryonic zebrafish. The structure of a PKD2 activating mutant F604P by cryo-electron microscopy reveals a pi- to alpha-helix transition within the pore-lining helix S6 that leads to repositioning of the gate residue and channel activation. Overall the results identify hydrophobic gates and a gating mechanism of PKD2 and PKD2L1. | |||
Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.,Zheng W, Yang X, Hu R, Cai R, Hofmann L, Wang Z, Hu Q, Liu X, Bulkey D, Yu Y, Tang J, Flockerzi V, Cao Y, Cao E, Chen XZ Nat Commun. 2018 Jun 13;9(1):2302. doi: 10.1038/s41467-018-04586-x. PMID:29899465<ref>PMID:29899465</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6d1w" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</SX> | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Bulkley, D]] | [[Category: Bulkley, D]] | ||
[[Category: Cao, E]] | [[Category: Cao, E]] | ||
[[Category: Chen, X Z]] | |||
[[Category: Yang, X]] | |||
[[Category: Zheng, W]] | [[Category: Zheng, W]] | ||
[[Category: Ion channel]] | |||
[[Category: Pc2]] | |||
[[Category: Pkd2]] | |||
[[Category: Transport protein]] | |||
[[Category: Trp channel]] | |||
[[Category: Trpp2]] | |||