8b8t: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8b8t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B8T FirstGlance]. <br> | <table><tr><td colspan='2'>[[8b8t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B8T FirstGlance]. <br> | ||
</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=8b8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b8t OCA], [https://pdbe.org/8b8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b8t RCSB], [https://www.ebi.ac.uk/pdbsum/8b8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b8t ProSAT]</span></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]] 4.2Å</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=8b8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b8t OCA], [https://pdbe.org/8b8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b8t RCSB], [https://www.ebi.ac.uk/pdbsum/8b8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b8t ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
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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 8b8t" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8b8t" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA ligase 3D structures|DNA ligase 3D structures]] | |||
*[[Proliferating cell nuclear antigen 3D structures|Proliferating cell nuclear antigen 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 09:47, 24 July 2024
Open conformation of the complex of DNA ligase I on PCNA and DNA in the presence of ATPOpen conformation of the complex of DNA ligase I on PCNA and DNA in the presence of ATP
Structural highlights
FunctionDNLI1_HUMAN DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair. Publication Abstract from PubMedDuring 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, Crehuet R, Hamdan SM, De Biasio A Nat Commun. 2022 Dec 20;13(1):7833. doi: 10.1038/s41467-022-35475-z. PMID:36539424[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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