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1u76

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Revision as of 18:15, 25 December 2014

Crystal structure of hPCNA bound to residues 452-466 of the DNA polymerase-delta-p66 subunit

Structural highlights

1u76 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1u7b
Gene:	PCNA (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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] [DPOD3_HUMAN] Required for optimal DNA polymerase delta activity.^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human Proliferating Cellular Nuclear Antigen (hPCNA), a member of the sliding clamp family of proteins, makes specific protein-protein interactions with DNA replication and repair proteins through a small peptide motif termed the PCNA-interacting protein, or PIP-box. We solved the structure of hPCNA bound to PIP-box-containing peptides from the p66 subunit of the human replicative DNA polymerase-delta (452-466) at 2.6 A and of the flap endonuclease (FEN1) (331-350) at 1.85 A resolution. Both structures demonstrate that the pol-delta p66 and FEN1 peptides interact with hPCNA at the same site shown to bind the cdk-inhibitor p21(CIP1). Binding studies indicate that peptides from the p66 subunit of the pol-delta holoenzyme and FEN1 bind hPCNA from 189- to 725-fold less tightly than those of p21. Thus, the PIP-box and flanking regions provide a small docking peptide whose affinities can be readily adjusted in accord with biological necessity to mediate the binding of DNA replication and repair proteins to hPCNA.

Structural and thermodynamic analysis of human PCNA with peptides derived from DNA polymerase-delta p66 subunit and flap endonuclease-1.,Bruning JB, Shamoo Y Structure. 2004 Dec;12(12):2209-19. PMID:15576034^[6]

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
↑ Hughes P, Tratner I, Ducoux M, Piard K, Baldacci G. Isolation and identification of the third subunit of mammalian DNA polymerase delta by PCNA-affinity chromatography of mouse FM3A cell extracts. Nucleic Acids Res. 1999 May 15;27(10):2108-14. PMID:10219083
↑ Mo J, Liu L, Leon A, Mazloum N, Lee MY. Evidence that DNA polymerase delta isolated by immunoaffinity chromatography exhibits high-molecular weight characteristics and is associated with the KIAA0039 protein and RPA. Biochemistry. 2000 Jun 20;39(24):7245-54. PMID:10852724
↑ Li H, Xie B, Zhou Y, Rahmeh A, Trusa S, Zhang S, Gao Y, Lee EY, Lee MY. Functional roles of p12, the fourth subunit of human DNA polymerase delta. J Biol Chem. 2006 May 26;281(21):14748-55. Epub 2006 Feb 28. PMID:16510448 doi:http://dx.doi.org/10.1074/jbc.M600322200
↑ Bruning JB, Shamoo Y. Structural and thermodynamic analysis of human PCNA with peptides derived from DNA polymerase-delta p66 subunit and flap endonuclease-1. Structure. 2004 Dec;12(12):2209-19. PMID:15576034 doi:http://dx.doi.org/10.1016/j.str.2004.09.018

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1u76"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1u76]] is a 6 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=1U76 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U76 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u7b|1u7b]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u7b|1u7b]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PCNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PCNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u76 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1u76 RCSB], [http://www.ebi.ac.uk/pdbsum/1u76 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u76 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1u76 RCSB], [http://www.ebi.ac.uk/pdbsum/1u76 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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>  [[http://www.uniprot.org/uniprot/DPOD3_HUMAN DPOD3_HUMAN]] Required for optimal DNA polymerase delta activity.<ref>PMID:10219083</ref> <ref>PMID:10852724</ref> <ref>PMID:16510448</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bruning, J B.]]
+[[Category: Bruning, J B]]
-[[Category: Shamoo, Y.]]
+[[Category: Shamoo, Y]]
 [[Category: Dna polymerase delta]]
 [[Category: Dna replication]]

1u76

From Proteopedia

Revision as of 18:15, 25 December 2014

Crystal structure of hPCNA bound to residues 452-466 of the DNA polymerase-delta-p66 subunit

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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