6qh1

The structure of Schizosaccharomyces pombe PCNA in complex with an Spd1 derived peptide

spinqualitylabelsall models 6qh1, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qh1 is a 4 chain structure with sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PCNA_SCHPO This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Publication Abstract from PubMed DNA regulation, replication and repair are processes fundamental to all known organisms and the sliding clamp proliferating cell nuclear antigen (PCNA) is central to all these processes. S-phase delaying protein 1 (Spd1) from S. pombe, an intrinsically disordered protein that causes checkpoint activation by inhibiting the enzyme ribonucleotide reductase, has one of the most divergent PCNA binding motifs known. Using NMR spectroscopy, in vivo assays, X-ray crystallography, calorimetry, and Monte Carlo simulations, an additional PCNA binding motif in Spd1, a PIP-box, is revealed. The two tandemly positioned, low affinity sites exchange rapidly on PCNA exploiting the same binding sites. Increasing or decreasing the binding affinity between Spd1 and PCNA through mutations of either motif compromised the ability of Spd1 to cause checkpoint activation in yeast. These results pinpoint a role for PCNA in Spd1-mediated checkpoint activation and suggest that its tandemly positioned short linear motifs create a neatly balanced competition-based system, involving PCNA, Spd1 and the small ribonucleotide reductase subunit, Suc22R2. Similar mechanisms may be relevant in other PCNA binding ligands where divergent binding motifs so far have gone under the PIP-box radar. Checkpoint activation by Spd1: a competition-based system relying on tandem disordered PCNA binding motifs.,Olsen JG, Prestel A, Kassem N, Broendum SS, Shamim HM, Simonsen S, Grysbaek M, Mortensen J, Rytkjaer LL, Haxholm GW, Marabini R, Holmberg C, Carr AM, Crehuet R, Nielsen O, Kragelund BB Nucleic Acids Res. 2024 Feb 28;52(4):2030-2044. doi: 10.1093/nar/gkae011. PMID:38261971 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proliferating cell nuclear antigen 3D structures

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