View source for 8uyf


==Structure of nucleotide-free Pediculus humanus (Ph) PINK1 dimer==
<StructureSection load='8uyf' size='340' side='right'caption='[[8uyf]], [[Resolution|resolution]] 2.75&Aring;' 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]] 2.75&#8491;</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8uyf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pediculus humanus corporis]]
[[Category: Gan ZY]]
[[Category: Kirk NS]]
[[Category: Komander D]]
[[Category: Leis A]]