3p87

From Proteopedia

(Difference between revisions)

Current revision

Structure of human PCNA bound to RNASEH2B PIP box peptide

Structural highlights

3p87 is a 12 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:	X-ray diffraction, Resolution 2.99Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PCNA_HUMAN Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.^[1] ^[2]

Publication Abstract from PubMed

Ribonuclease H2 is the major nuclear enzyme degrading cellular RNA/DNA hybrids in eukaryotes and the sole nuclease known to be able to hydrolyze ribonucleotides misincorporated during genomic replication. Mutation in RNASEH2 causes Aicardi-Goutieres syndrome, an auto-inflammatory disorder that may arise from nucleic acid byproducts generated during DNA replication. Here, we report the crystal structures of Archaeoglobus fulgidus RNase HII in complex with PCNA, and human PCNA bound to a C-terminal peptide of RNASEH2B. In the archaeal structure, three binding modes are observed as the enzyme rotates about a flexible hinge while anchored to PCNA by its PIP-box motif. PCNA binding promotes RNase HII activity in a hinge-dependent manner. It enhances both cleavage of ribonucleotides misincorporated in DNA duplexes, and the comprehensive hydrolysis of RNA primers formed during Okazaki fragment maturation. In addition, PCNA imposes strand specificity on enzyme function, and by localizing RNase H2 and not RNase H1 to nuclear replication foci in vivo it ensures that RNase H2 is the dominant RNase H activity during nuclear replication. Our findings provide insights into how type 2 RNase H activity is directed during genome replication and repair, and suggest a mechanism by which RNase H2 may suppress generation of immunostimulatory nucleic acids.

PCNA directs type 2 RNase H activity on DNA replication and repair substrates.,Bubeck D, Reijns MA, Graham SC, Astell KR, Jones EY, Jackson AP Nucleic Acids Res. 2011 Jan 17. PMID:21245041^[3]

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

References

↑ Burkovics P, Hajdu I, Szukacsov V, Unk I, Haracska L. Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage. Nucleic Acids Res. 2009 Jul;37(13):4247-55. doi: 10.1093/nar/gkp357. Epub 2009, May 13. PMID:19443450 doi:10.1093/nar/gkp357
↑ Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6. Epub 2008 Aug 21. PMID:18719106 doi:0805685105
↑ Bubeck D, Reijns MA, Graham SC, Astell KR, Jones EY, Jackson AP. PCNA directs type 2 RNase H activity on DNA replication and repair substrates. Nucleic Acids Res. 2011 Jan 17. PMID:21245041 doi:10.1093/nar/gkq980

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3p87"

@@ Line 1: / Line 1: @@
-[[Image:3p87.png|left|200px]]
-{{STRUCTURE_3p87|  PDB=3p87  |  SCENE=  }}
+==Structure of human PCNA bound to RNASEH2B PIP box peptide==
+<StructureSection load='3p87' size='340' side='right'caption='[[3p87]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3p87]] is a 12 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=3P87 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P87 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.99&#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=3p87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p87 OCA], [https://pdbe.org/3p87 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p87 RCSB], [https://www.ebi.ac.uk/pdbsum/3p87 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p87 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PCNA_HUMAN PCNA_HUMAN] Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.<ref>PMID:19443450</ref> <ref>PMID:18719106</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ribonuclease H2 is the major nuclear enzyme degrading cellular RNA/DNA hybrids in eukaryotes and the sole nuclease known to be able to hydrolyze ribonucleotides misincorporated during genomic replication. Mutation in RNASEH2 causes Aicardi-Goutieres syndrome, an auto-inflammatory disorder that may arise from nucleic acid byproducts generated during DNA replication. Here, we report the crystal structures of Archaeoglobus fulgidus RNase HII in complex with PCNA, and human PCNA bound to a C-terminal peptide of RNASEH2B. In the archaeal structure, three binding modes are observed as the enzyme rotates about a flexible hinge while anchored to PCNA by its PIP-box motif. PCNA binding promotes RNase HII activity in a hinge-dependent manner. It enhances both cleavage of ribonucleotides misincorporated in DNA duplexes, and the comprehensive hydrolysis of RNA primers formed during Okazaki fragment maturation. In addition, PCNA imposes strand specificity on enzyme function, and by localizing RNase H2 and not RNase H1 to nuclear replication foci in vivo it ensures that RNase H2 is the dominant RNase H activity during nuclear replication. Our findings provide insights into how type 2 RNase H activity is directed during genome replication and repair, and suggest a mechanism by which RNase H2 may suppress generation of immunostimulatory nucleic acids.
-===Structure of human PCNA bound to RNASEH2B PIP box peptide===
+PCNA directs type 2 RNase H activity on DNA replication and repair substrates.,Bubeck D, Reijns MA, Graham SC, Astell KR, Jones EY, Jackson AP Nucleic Acids Res. 2011 Jan 17. PMID:21245041<ref>PMID:21245041</ref>
-{{ABSTRACT_PUBMED_21245041}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3p87" style="background-color:#fffaf0;"></div>
-[[3p87]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P87 OCA].
 ==See Also==
-*[[Proliferating Cell Nuclear Antigen|Proliferating Cell Nuclear Antigen]]
+*[[Proliferating cell nuclear antigen 3D structures|Proliferating cell nuclear antigen 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:021245041</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Astell, K R.]]
+[[Category: Large Structures]]
-[[Category: Bubeck, D.]]
+[[Category: Astell KR]]
-[[Category: Graham, S C.]]
+[[Category: Bubeck D]]
-[[Category: Jackson, A P.]]
+[[Category: Graham SC]]
-[[Category: Jones, E Y.]]
+[[Category: Jackson AP]]
-[[Category: Reijns, M A.]]
+[[Category: Jones EY]]
-[[Category: Dna binding]]
+[[Category: Reijns MA]]
-[[Category: Dna clamp]]
-[[Category: Dna repair]]
-[[Category: Dna replication]]
-[[Category: Fen-1]]
-[[Category: Helicase]]
-[[Category: Hydrolase-dna binding protein complex]]
-[[Category: Ligase]]
-[[Category: Nuclease]]
-[[Category: Nucleus]]
-[[Category: Pip-box motif]]
-[[Category: Polymerase]]
-[[Category: Processivity factor]]
-[[Category: Rnase h2]]
-[[Category: Sliding clamp]]

3p87

From Proteopedia

Current revision

Structure of human PCNA bound to RNASEH2B PIP box peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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