8uyf

Structure of nucleotide-free Pediculus humanus (Ph) PINK1 dimer

spinqualitylabelsall models 8uyf, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8uyf is a 2 chain structure with sequence from Pediculus humanus corporis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.75Å Ligands: TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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