8yjz

From Proteopedia

(Difference between revisions)

Current revision

Structure of the human endogenous PCNA-FEN1-RNase H2 complex - State D

Structural highlights

8yjz is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 5.15Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

RNH2A_HUMAN Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

RNH2A_HUMAN Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.^[1] ^[2]

Publication Abstract from PubMed

PCNA is a master coordinator of many DNA-metabolic events. During DNA replication, the maturation of Okazaki fragments involves at least four DNA enzymes, all of which contain PCNA-interacting motifs. However, the temporal relationships and functional modulations between these PCNA-binding proteins are unclear. Here, we developed a strategy to purify endogenous PCNA-containing complexes from native chromatin, and characterized their structures using cryo-EM. Two structurally resolved classes (PCNA-FEN1 and PCNA-FEN1-RNaseH2 complexes) have captured a series of 3D snapshots for the primer-removal steps of Okazaki fragment maturation. These structures show that product release from FEN1 is a rate-liming step. Furthermore, both FEN1 and RNaseH2 undergo continuous conformational changes on PCNA that result in constant fluctuations in the bending angle of substrate DNA at the nick site, implying that these enzymes could regulate each other through conformational modulation of the bound DNA. The structures of the PCNA-FEN1-RNaseH2 complex confirm the toolbelt function of PCNA and suggests a potential unrecognized role of RNaseH2, as a dsDNA binding protein, in promoting the 5'-flap cleaving activity of FEN1.

Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2.,Tian Y, Li N, Li Q, Gao N EMBO J. 2024 Nov 22. doi: 10.1038/s44318-024-00296-x. PMID:39578540^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Crow YJ, Leitch A, Hayward BE, Garner A, Parmar R, Griffith E, Ali M, Semple C, Aicardi J, Babul-Hirji R, Baumann C, Baxter P, Bertini E, Chandler KE, Chitayat D, Cau D, Dery C, Fazzi E, Goizet C, King MD, Klepper J, Lacombe D, Lanzi G, Lyall H, Martinez-Frias ML, Mathieu M, McKeown C, Monier A, Oade Y, Quarrell OW, Rittey CD, Rogers RC, Sanchis A, Stephenson JB, Tacke U, Till M, Tolmie JL, Tomlin P, Voit T, Weschke B, Woods CG, Lebon P, Bonthron DT, Ponting CP, Jackson AP. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection. Nat Genet. 2006 Aug;38(8):910-6. Epub 2006 Jul 16. PMID:16845400 doi:http://dx.doi.org/10.1038/ng1842
↑ Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M. The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects. J Biol Chem. 2011 Mar 25;286(12):10540-50. Epub 2010 Dec 22. PMID:21177858 doi:10.1074/jbc.M110.181974
↑ Tian Y, Li N, Li Q, Gao N. Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2. EMBO J. 2024 Nov 22. PMID:39578540 doi:10.1038/s44318-024-00296-x

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8yjz"

Categories: Homo sapiens | Large Structures | Gao N | Tian Y

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8yjz is ON HOLD  until Paper Publication
+==Structure of the human endogenous PCNA-FEN1-RNase H2 complex - State D==
+<StructureSection load='8yjz' size='340' side='right'caption='[[8yjz]], [[Resolution|resolution]] 5.15&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8yjz]] is a 10 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=8YJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8YJZ FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.15&#8491;</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=8yjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8yjz OCA], [https://pdbe.org/8yjz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8yjz RCSB], [https://www.ebi.ac.uk/pdbsum/8yjz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8yjz ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/RNH2A_HUMAN RNH2A_HUMAN] Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/RNH2A_HUMAN RNH2A_HUMAN] Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.<ref>PMID:16845400</ref> <ref>PMID:21177858</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+PCNA is a master coordinator of many DNA-metabolic events. During DNA replication, the maturation of Okazaki fragments involves at least four DNA enzymes, all of which contain PCNA-interacting motifs. However, the temporal relationships and functional modulations between these PCNA-binding proteins are unclear. Here, we developed a strategy to purify endogenous PCNA-containing complexes from native chromatin, and characterized their structures using cryo-EM. Two structurally resolved classes (PCNA-FEN1 and PCNA-FEN1-RNaseH2 complexes) have captured a series of 3D snapshots for the primer-removal steps of Okazaki fragment maturation. These structures show that product release from FEN1 is a rate-liming step. Furthermore, both FEN1 and RNaseH2 undergo continuous conformational changes on PCNA that result in constant fluctuations in the bending angle of substrate DNA at the nick site, implying that these enzymes could regulate each other through conformational modulation of the bound DNA. The structures of the PCNA-FEN1-RNaseH2 complex confirm the toolbelt function of PCNA and suggests a potential unrecognized role of RNaseH2, as a dsDNA binding protein, in promoting the 5'-flap cleaving activity of FEN1.
-Authors: Tian, Y., Gao, N.
+Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2.,Tian Y, Li N, Li Q, Gao N EMBO J. 2024 Nov 22. doi: 10.1038/s44318-024-00296-x. PMID:39578540<ref>PMID:39578540</ref>
-Description: endogenous state D PCNA-DNA-FEN1-RNase H2 complex
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Tian, Y]]
+<div class="pdbe-citations 8yjz" style="background-color:#fffaf0;"></div>
-[[Category: Gao, N]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Gao N]]
+[[Category: Tian Y]]

8yjz

From Proteopedia

Current revision

Structure of the human endogenous PCNA-FEN1-RNase H2 complex - State D

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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