5mav

From Proteopedia

(Difference between revisions)

Revision as of 06:35, 16 October 2019

Crystal structure of human PCNA in complex with PARG (poly(ADP-ribose) glycohydrolase) peptide.

Structural highlights

5mav is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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

Poly(ADP-ribose) glycohydrolase (PARG) regulates cellular poly(ADP-ribose) (PAR) levels by rapidly cleaving glycosidic bonds between ADP-ribose units. PARG interacts with proliferating cell nuclear antigen (PCNA) and is strongly recruited to DNA damage sites in a PAR- and PCNA-dependent fashion. Here we identified PARG acetylation site K409 that is essential for its interaction with PCNA, its localization within replication foci and its recruitment to DNA damage sites. We found K409 to be part of a non-canonical PIP-box within the PARG disordered regulatory region. The previously identified putative N-terminal PIP-box does not bind PCNA directly but contributes to PARG localization within replication foci. X-ray structure and MD simulations reveal that the PARG non-canonical PIP-box binds PCNA in a manner similar to other canonical PIP-boxes and may represent a new type of PIP-box. While the binding of previously described PIP-boxes is based on hydrophobic interactions, PARG PIP-box binds PCNA via both stabilizing hydrophobic and fine-tuning electrostatic interactions. Our data explain the mechanism of PARG-PCNA interaction through a new PARG PIP-box that exhibits non-canonical sequence properties but a canonical mode of PCNA binding.

A novel non-canonical PIP-box mediates PARG interaction with PCNA.,Kaufmann T, Grishkovskaya I, Polyansky AA, Kostrhon S, Kukolj E, Olek KM, Herbert S, Beltzung E, Mechtler K, Peterbauer T, Gotzmann J, Zhang L, Hartl M, Zagrovic B, Elsayad K, Djinovic-Carugo K, Slade D Nucleic Acids Res. 2017 Sep 19;45(16):9741-9759. doi: 10.1093/nar/gkx604. PMID:28934471^[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
↑ Kaufmann T, Grishkovskaya I, Polyansky AA, Kostrhon S, Kukolj E, Olek KM, Herbert S, Beltzung E, Mechtler K, Peterbauer T, Gotzmann J, Zhang L, Hartl M, Zagrovic B, Elsayad K, Djinovic-Carugo K, Slade D. A novel non-canonical PIP-box mediates PARG interaction with PCNA. Nucleic Acids Res. 2017 Sep 19;45(16):9741-9759. doi: 10.1093/nar/gkx604. PMID:28934471 doi:http://dx.doi.org/10.1093/nar/gkx604

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/5mav"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human PCNA in complex with PARG (poly(ADP-ribose) glycohydrolase) peptide.==
-<StructureSection load='5mav' size='340' side='right' caption='[[5mav]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
+<StructureSection load='5mav' size='340' side='right'caption='[[5mav]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5mav]] is a 12 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=5MAV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MAV FirstGlance]. <br>
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 5mav" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Proliferating Cell Nuclear Antigen|Proliferating Cell Nuclear Antigen]]
 == References ==
 <references/>
@@ Line 23: / Line 26: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Djinovic-Carugo, K]]
 [[Category: Grishkovskaya, I]]

5mav

From Proteopedia

Revision as of 06:35, 16 October 2019

Crystal structure of human PCNA in complex with PARG (poly(ADP-ribose) glycohydrolase) peptide.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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