8uyf
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 8uyf is ON HOLD until Paper Publication Authors: Gan, Z.Y., Kirk, N.S., Leis, A., Komander, D. Description: Structure of nucleotide-free Pediculus ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of nucleotide-free Pediculus humanus (Ph) PINK1 dimer== | |
| + | <StructureSection load='8uyf' size='340' side='right'caption='[[8uyf]], [[Resolution|resolution]] 2.75Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8uyf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pediculus_humanus_corporis Pediculus humanus corporis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UYF 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]] 2.75Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=8uyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uyf OCA], [https://pdbe.org/8uyf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uyf RCSB], [https://www.ebi.ac.uk/pdbsum/8uyf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uyf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The ubiquitin kinase PINK1 accumulates on damaged mitochondria to trigger mitophagy, and PINK1 loss-of-function mutations cause early onset Parkinson's disease. Nucleotide analogs such as kinetin triphosphate (KTP) were reported to enhance PINK1 activity and may represent a therapeutic strategy for the treatment of Parkinson's disease. Here, we investigate the interaction of PINK1 with nucleotides, including KTP. We establish a cryo-EM platform exploiting the dodecamer assembly of Pediculus humanus corporis (Ph) PINK1 and determine PINK1 structures bound to AMP-PNP and ADP, revealing conformational changes in the kinase N-lobe that help establish PINK1's ubiquitin binding site. Notably, we find that KTP is unable to bind PhPINK1 or human (Hs) PINK1 due to a steric clash with the kinase "gatekeeper" methionine residue, and mutation to Ala or Gly is required for PINK1 to bind and use KTP as a phosphate donor in ubiquitin phosphorylation and mitophagy. HsPINK1 M318G can be used to conditionally uncouple PINK1 stabilization and activity on mitochondria. | ||
| - | + | Interaction of PINK1 with nucleotides and kinetin.,Gan ZY, Callegari S, Nguyen TN, Kirk NS, Leis A, Lazarou M, Dewson G, Komander D Sci Adv. 2024 Jan 19;10(3):eadj7408. doi: 10.1126/sciadv.adj7408. Epub 2024 Jan , 19. PMID:38241364<ref>PMID:38241364</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8uyf" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Kirk | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pediculus humanus corporis]] | ||
| + | [[Category: Gan ZY]] | ||
| + | [[Category: Kirk NS]] | ||
| + | [[Category: Komander D]] | ||
| + | [[Category: Leis A]] | ||
Current revision
Structure of nucleotide-free Pediculus humanus (Ph) PINK1 dimer
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