8b8t
From Proteopedia
(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> | ||
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| + | ==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/> | ||
Current revision
Open conformation of the complex of DNA ligase I on PCNA and DNA in the presence of ATP
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Categories: Homo sapiens | Large Structures | Blair K | Cruehet R | De Biasio A | Hamdan S | Lancey C | Raducanu VS | Shahid T | Tehseen M
