8uyf: Difference between revisions
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==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]] | |||
Latest revision as of 10:02, 9 October 2024
Structure of nucleotide-free Pediculus humanus (Ph) PINK1 dimer
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