5iy4

From Proteopedia

(Difference between revisions)

Revision as of 10:37, 6 September 2023

Crystal structure of human PCNA in complex with the PIP box of DVC1

Structural highlights

5iy4 is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.945Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SPRTN_HUMAN Progeroid features-hepatocellular carcinoma predisposition syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

SPRTN_HUMAN Regulator of UV-induced DNA damage response: acts as a 'reader' of ubiquitinated PCNA that enhances RAD18-mediated PCNA ubiquitination and translesion DNA synthesis (TLS). Recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis. Acts as a regulator of TLS by recruiting VCP/p97 to sites of DNA damage, possibly leading to extraction of DNA polymerase eta (POLH) by VCP/p97 to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

In higher eukaryotes, DVC1 (SPRTN, Spartan or C1orf124) is implicated in the translesion synthesis (TLS) pathway. DVC1 localizes to sites of DNA damage, binds to the proliferating cell nuclear antigen (PCNA) via its conserved PCNA-interacting motif (PIP box), and associates with ubiquitin selective segregase p97 and other factors, thus regulating translesion synthesis polymerases. Here, we report the crystal structure of human PCNA in complex with a peptide ((321)SNSHQNVLSNYFPRVS(336)) derived from human DVC1 that contains a unique YF type PIP box. Structural analysis reveals the detailed PIP box-PCNA interaction. Interestingly, substitution of Y331 with Phe severely reduces its PCNA binding affinity. These findings offer new insights into the determinants of PIP box for PCNA binding.

Crystal structure of human PCNA in complex with the PIP box of DVC1.,Wang Y, Xu M, Jiang T Biochem Biophys Res Commun. 2016 May 27;474(2):264-70. doi:, 10.1016/j.bbrc.2016.04.053. Epub 2016 Apr 13. PMID:27084448^[7]

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

References

↑ Centore RC, Yazinski SA, Tse A, Zou L. Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response. Mol Cell. 2012 Jun 8;46(5):625-35. doi: 10.1016/j.molcel.2012.05.020. PMID:22681887 doi:http://dx.doi.org/10.1016/j.molcel.2012.05.020
↑ Machida Y, Kim MS, Machida YJ. Spartan/C1orf124 is important to prevent UV-induced mutagenesis. Cell Cycle. 2012 Sep 15;11(18):3395-402. doi: 10.4161/cc.21694. Epub 2012 Aug 16. PMID:22894931 doi:http://dx.doi.org/10.4161/cc.21694
↑ Ghosal G, Leung JW, Nair BC, Fong KW, Chen J. Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis. J Biol Chem. 2012 Oct 5;287(41):34225-33. doi: 10.1074/jbc.M112.400135. Epub 2012, Aug 17. PMID:22902628 doi:http://dx.doi.org/10.1074/jbc.M112.400135
↑ Juhasz S, Balogh D, Hajdu I, Burkovics P, Villamil MA, Zhuang Z, Haracska L. Characterization of human Spartan/C1orf124, an ubiquitin-PCNA interacting regulator of DNA damage tolerance. Nucleic Acids Res. 2012 Nov;40(21):10795-808. doi: 10.1093/nar/gks850. Epub 2012 , Sep 16. PMID:22987070 doi:http://dx.doi.org/10.1093/nar/gks850
↑ Mosbech A, Gibbs-Seymour I, Kagias K, Thorslund T, Beli P, Povlsen L, Nielsen SV, Smedegaard S, Sedgwick G, Lukas C, Hartmann-Petersen R, Lukas J, Choudhary C, Pocock R, Bekker-Jensen S, Mailand N. DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks. Nat Struct Mol Biol. 2012 Nov;19(11):1084-92. doi: 10.1038/nsmb.2395. Epub 2012, Oct 7. PMID:23042605 doi:10.1038/nsmb.2395
↑ Davis EJ, Lachaud C, Appleton P, Macartney TJ, Nathke I, Rouse J. DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage. Nat Struct Mol Biol. 2012 Nov;19(11):1093-100. doi: 10.1038/nsmb.2394. Epub 2012 , Oct 7. PMID:23042607 doi:10.1038/nsmb.2394
↑ Wang Y, Xu M, Jiang T. Crystal structure of human PCNA in complex with the PIP box of DVC1. Biochem Biophys Res Commun. 2016 May 27;474(2):264-70. doi:, 10.1016/j.bbrc.2016.04.053. Epub 2016 Apr 13. PMID:27084448 doi:http://dx.doi.org/10.1016/j.bbrc.2016.04.053

1 Structural highlights
2 Disease
3 Function
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/5iy4"

@@ Line 3: / Line 3: @@
 <StructureSection load='5iy4' size='340' side='right'caption='[[5iy4]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5iy4]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IY4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IY4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5iy4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IY4 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5iy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iy4 OCA], [http://pdbe.org/5iy4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iy4 RCSB], [http://www.ebi.ac.uk/pdbsum/5iy4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iy4 ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.945&#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=5iy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iy4 OCA], [https://pdbe.org/5iy4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iy4 RCSB], [https://www.ebi.ac.uk/pdbsum/5iy4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iy4 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SPRTN_HUMAN SPRTN_HUMAN] Progeroid features-hepatocellular carcinoma predisposition syndrome. The disease is caused by mutations affecting the gene represented in this entry.
 == 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>
+[https://www.uniprot.org/uniprot/SPRTN_HUMAN SPRTN_HUMAN] Regulator of UV-induced DNA damage response: acts as a 'reader' of ubiquitinated PCNA that enhances RAD18-mediated PCNA ubiquitination and translesion DNA synthesis (TLS). Recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis. Acts as a regulator of TLS by recruiting VCP/p97 to sites of DNA damage, possibly leading to extraction of DNA polymerase eta (POLH) by VCP/p97 to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.<ref>PMID:22681887</ref> <ref>PMID:22894931</ref> <ref>PMID:22902628</ref> <ref>PMID:22987070</ref> <ref>PMID:23042605</ref> <ref>PMID:23042607</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Jiang, T]]
+[[Category: Synthetic construct]]
-[[Category: Wang, Y]]
+[[Category: Jiang T]]
-[[Category: Xu, M]]
+[[Category: Wang Y]]
-[[Category: Dna binding protein]]
+[[Category: Xu M]]
-[[Category: Dvc1]]
-[[Category: Pcna]]
-[[Category: Pip box]]

5iy4

From Proteopedia

Revision as of 10:37, 6 September 2023

Crystal structure of human PCNA in complex with the PIP box of DVC1

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox