7qo1: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7qo1]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QO1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7qo1]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QO1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</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=7qo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qo1 OCA], [https://pdbe.org/7qo1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qo1 RCSB], [https://www.ebi.ac.uk/pdbsum/7qo1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qo1 ProSAT]</span></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=7qo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qo1 OCA], [https://pdbe.org/7qo1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qo1 RCSB], [https://www.ebi.ac.uk/pdbsum/7qo1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qo1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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During lagging strand synthesis, DNA Ligase 1 (Lig1) cooperates with the sliding clamp PCNA to seal the nicks between Okazaki fragments generated by Pol delta and Flap endonuclease 1 (FEN1). We present several cryo-EM structures combined with functional assays, showing that human Lig1 recruits PCNA to nicked DNA using two PCNA-interacting motifs (PIPs) located at its disordered N-terminus (PIP(N-term)) and DNA binding domain (PIP(DBD)). Once Lig1 and PCNA assemble as two-stack rings encircling DNA, PIP(N-term) is released from PCNA and only PIP(DBD) is required for ligation to facilitate the substrate handoff from FEN1. Consistently, we observed that PCNA forms a defined complex with FEN1 and nicked DNA, and it recruits Lig1 to an unoccupied monomer creating a toolbelt that drives the transfer of DNA to Lig1. Collectively, our results provide a structural model on how PCNA regulates FEN1 and Lig1 during Okazaki fragments maturation. | During lagging strand synthesis, DNA Ligase 1 (Lig1) cooperates with the sliding clamp PCNA to seal the nicks between Okazaki fragments generated by Pol delta and Flap endonuclease 1 (FEN1). We present several cryo-EM structures combined with functional assays, showing that human Lig1 recruits PCNA to nicked DNA using two PCNA-interacting motifs (PIPs) located at its disordered N-terminus (PIP(N-term)) and DNA binding domain (PIP(DBD)). Once Lig1 and PCNA assemble as two-stack rings encircling DNA, PIP(N-term) is released from PCNA and only PIP(DBD) is required for ligation to facilitate the substrate handoff from FEN1. Consistently, we observed that PCNA forms a defined complex with FEN1 and nicked DNA, and it recruits Lig1 to an unoccupied monomer creating a toolbelt that drives the transfer of DNA to Lig1. Collectively, our results provide a structural model on how PCNA regulates FEN1 and Lig1 during Okazaki fragments maturation. | ||
Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing.,Blair K, Tehseen M, Raducanu VS, Shahid T, Lancey C, Rashid F, | Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing.,Blair K, Tehseen M, Raducanu VS, Shahid T, Lancey C, Rashid F, Crehuet R, Hamdan SM, De Biasio A Nat Commun. 2022 Dec 20;13(1):7833. doi: 10.1038/s41467-022-35475-z. PMID:36539424<ref>PMID:36539424</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7qo1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7qo1" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA ligase 3D structures|DNA ligase 3D structures]] | |||
*[[Endonuclease 3D structures|Endonuclease 3D structures]] | |||
*[[Proliferating cell nuclear antigen 3D structures|Proliferating cell nuclear antigen 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 12:38, 17 July 2024
complex of DNA ligase I and FEN1 on PCNA and DNA
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