5e0v

From Proteopedia

(Difference between revisions)

Revision as of 12:32, 16 November 2017

Human PCNA variant (S228I) complexed with FEN1 at 2.1 Angstroms

Structural highlights

5e0v is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1axc, 5e0t, 5e0u
Gene:	PCNA (HUMAN)
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

The eukaryotic DNA polymerase sliding clamp, proliferating cell nuclear antigen or PCNA, is a ring-shaped protein complex that surrounds DNA to act as a sliding platform for increasing processivity of cellular replicases and for coordinating various cellular pathways with DNA replication. A single point mutation, Ser228Ile, in the human PCNA gene was recently identified to cause a disease whose symptoms resemble those of DNA damage and repair disorders. The mutation lies near the binding site for most PCNA-interacting proteins. However, the structural consequences of the S228I mutation are unknown. Here, we describe the structure of the disease-causing variant, which reveals a large conformational change that dramatically transforms the binding pocket for PCNA client proteins. We show that the mutation markedly alters the binding energetics for some client proteins, while another, p21(CIP1), is only mildly affected. Structures of the disease variant bound to peptides derived from two PCNA partner proteins reveal that the binding pocket can adjust conformation to accommodate some ligands, indicating that the binding site is dynamic and pliable. Our work has implications for the plasticity of the binding site in PCNA and reveals how a disease mutation selectively alters interactions to a promiscuous binding site that is critical for DNA metabolism.

A Disease-Causing Variant in PCNA Disrupts a Promiscuous Protein Binding Site.,Duffy CM, Hilbert BJ, Kelch BA J Mol Biol. 2016 Mar 27;428(6):1023-40. doi: 10.1016/j.jmb.2015.11.029. Epub 2015, Dec 11. PMID:26688547^[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
↑ Duffy CM, Hilbert BJ, Kelch BA. A Disease-Causing Variant in PCNA Disrupts a Promiscuous Protein Binding Site. J Mol Biol. 2016 Mar 27;428(6):1023-40. doi: 10.1016/j.jmb.2015.11.029. Epub 2015, Dec 11. PMID:26688547 doi:http://dx.doi.org/10.1016/j.jmb.2015.11.029

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e0v"

@@ Line 3: / Line 3: @@
 <StructureSection load='5e0v' size='340' side='right' caption='[[5e0v]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5e0v]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E0V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5e0v]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E0V FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1axc|1axc]], [[5e0t|5e0t]], [[5e0u|5e0u]]</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=5e0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0v OCA], [http://pdbe.org/5e0v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e0v RCSB], [http://www.ebi.ac.uk/pdbsum/5e0v PDBsum]</span></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 HUMAN])</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=5e0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0v OCA], [http://pdbe.org/5e0v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e0v RCSB], [http://www.ebi.ac.uk/pdbsum/5e0v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0v ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Duffy, C M]]
 [[Category: Hilbert, B J]]

5e0v

From Proteopedia

Revision as of 12:32, 16 November 2017

Human PCNA variant (S228I) complexed with FEN1 at 2.1 Angstroms

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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