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dc.contributor.authorYang, Dongxiao
dc.contributor.authorAlphey, Magnus S.
dc.contributor.authorMacNeill, Stuart
dc.identifier.citationYang , D , Alphey , M S & MacNeill , S 2022 , ' Non‐canonical binding of the Chaetomium thermophilum PolD4 N‐terminal PIP motif to PCNA involves Q‐pocket and compact 2‐fork plug interactions but no 3 10 helix ' , FEBS Journal , vol. Early View , 16590 .
dc.identifier.otherPURE: 280791702
dc.identifier.otherPURE UUID: a84ae62b-3220-4992-a874-f7eea69fcdef
dc.identifier.otherORCID: /0000-0002-9353-3716/work/117997478
dc.identifier.otherORCID: /0000-0002-0555-0007/work/117997530
dc.identifier.otherScopus: 85136459376
dc.identifier.otherWOS: 000843788200001
dc.descriptionFunding: Carnegie Trust for the Universities of Scotland (Grant Number(s): 70668). Chinese Scholarship Council.en
dc.description.abstractDNA polymerase δ (Pol δ) is a key enzyme for the maintenance of genome integrity in eukaryotic cells, acting in concert with the sliding clamp processivity factor PCNA (proliferating cell nuclear antigen). Three of the four subunits of human Pol δ interact directly with the PCNA homotrimer via a short, conserved protein sequence known as a PCNA interacting protein (PIP) motif. Here, we describe the identification of a PIP motif located towards the N-terminus of the PolD4 subunit of Pol δ (equivalent to human p12) from the thermophilic filamentous fungus Chaetomium thermophilum and present the X-ray crystal structure of the corresponding peptide bound to PCNA at 2.45 Å. Like human p12, the fungal PolD4 PIP motif displays non-canonical binding to PCNA. However, the structures of the human p12 and fungal PolD4 PIP motif peptides are quite distinct, with the fungal PolD4 PIP motif lacking the 310 helical segment that characterises most previously identified PIP motifs. Instead, the fungal PolD4 PIP motif binds PCNA via a conserved glutamine that inserts into the Q-pocket on the surface of PCNA and with conserved leucine and phenylalanine sidechains forming a compact 2-fork plug that inserts into the hydrophobic pocket on PCNA. Despite the unusual binding mode of the fungal PolD4, isothermal calorimetry (ITC) measurements show that its affinity for PCNA is similar to that of its human orthologue. These observations add to a growing body of information on how diverse proteins interact with PCNA and highlight how binding modes can vary significantly between orthologous PCNA partner proteins.
dc.relation.ispartofFEBS Journalen
dc.rightsCopyright © 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectDNA polymerase zetaen
dc.subjectDNA replicationen
dc.subjectChaetomium thermophilumen
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.titleNon‐canonical binding of the Chaetomium thermophilum PolD4 N‐terminal PIP motif to PCNA involves Q‐pocket and compact 2‐fork plug interactions but no 310 helixen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.description.statusPeer revieweden

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