7z5a

From Proteopedia

(Difference between revisions)

Revision as of 19:25, 19 October 2022

Crystal structure of the trapped complex of mouse Endonuclease VIII-LIKE 3 (mNEIL3) and hairpin DNA with 5'overhang

Structural highlights

7z5a is a 2 chain structure with sequence from Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NEIL3_MOUSE DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues. Seems to be an important facilitator of cell proliferation in certain populations, for example neural stem/progenitor cells and tumor cells, suggesting a role in replication-associated DNA repair.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Covalent DNA interstrand crosslinks are toxic DNA damage lesions that block the replication machinery that can cause a genomic instability. Ubiquitous abasic DNA sites are particularly susceptible to spontaneous cross-linking with a base from the opposite DNA strand. Detection of a crosslink induces the DNA helicase ubiquitination that recruits NEIL3, a DNA glycosylase responsible for the lesion removal. NEIL3 utilizes several zinc finger domains indispensable for its catalytic NEI domain repairing activity. They recruit NEIL3 to the repair site and bind the single-stranded DNA. However, the molecular mechanism underlying their roles in the repair process is unknown. Here, we report the structure of the tandem zinc-finger GRF domain of NEIL3 and reveal the molecular details of its interaction with DNA. Our biochemical data indicate the preferential binding of the GRF domain to the replication fork. In addition, we obtained a structure for the catalytic NEI domain in complex with the DNA reaction intermediate that allowed us to construct and validate a model for the interplay between the NEI and GRF domains in the recognition of an interstrand cross-link. Our results suggest a mechanism for recognition of the DNA replication X-structure by NEIL3, a key step in the interstrand cross-link repair.

Model of abasic site DNA cross-link repair; from the architecture of NEIL3 DNA binding domains to the X-structure model.,Huskova A, Dinesh DC, Srb P, Boura E, Veverka V, Silhan J Nucleic Acids Res. 2022 Oct 14;50(18):10436-10448. doi: 10.1093/nar/gkac793. PMID:36155818^[7]

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

References

↑ Liu M, Bandaru V, Bond JP, Jaruga P, Zhao X, Christov PP, Burrows CJ, Rizzo CJ, Dizdaroglu M, Wallace SS. The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4925-30. doi:, 10.1073/pnas.0908307107. Epub 2010 Feb 25. PMID:20185759 doi:http://dx.doi.org/10.1073/pnas.0908307107
↑ Sejersted Y, Hildrestrand GA, Kunke D, Rolseth V, Krokeide SZ, Neurauter CG, Suganthan R, Atneosen-Asegg M, Fleming AM, Saugstad OD, Burrows CJ, Luna L, Bjoras M. Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18802-7. doi:, 10.1073/pnas.1106880108. Epub 2011 Nov 7. PMID:22065741 doi:http://dx.doi.org/10.1073/pnas.1106880108
↑ Liu M, Bandaru V, Holmes A, Averill AM, Cannan W, Wallace SS. Expression and purification of active mouse and human NEIL3 proteins. Protein Expr Purif. 2012 Jul;84(1):130-9. doi: 10.1016/j.pep.2012.04.022. Epub, 2012 May 5. PMID:22569481 doi:http://dx.doi.org/10.1016/j.pep.2012.04.022
↑ Regnell CE, Hildrestrand GA, Sejersted Y, Medin T, Moldestad O, Rolseth V, Krokeide SZ, Suganthan R, Luna L, Bjoras M, Bergersen LH. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells. Cell Rep. 2012 Sep 27;2(3):503-10. doi: 10.1016/j.celrep.2012.08.008. Epub 2012, Sep 6. PMID:22959434 doi:http://dx.doi.org/10.1016/j.celrep.2012.08.008
↑ Rolseth V, Krokeide SZ, Kunke D, Neurauter CG, Suganthan R, Sejersted Y, Hildrestrand GA, Bjoras M, Luna L. Loss of Neil3, the major DNA glycosylase activity for removal of hydantoins in single stranded DNA, reduces cellular proliferation and sensitizes cells to genotoxic stress. Biochim Biophys Acta. 2013 May;1833(5):1157-64. doi:, 10.1016/j.bbamcr.2012.12.024. Epub 2013 Jan 7. PMID:23305905 doi:http://dx.doi.org/10.1016/j.bbamcr.2012.12.024
↑ Liu M, Imamura K, Averill AM, Wallace SS, Doublie S. Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA. Structure. 2013 Feb 5;21(2):247-56. doi: 10.1016/j.str.2012.12.008. Epub 2013 Jan, 9. PMID:23313161 doi:http://dx.doi.org/10.1016/j.str.2012.12.008
↑ Huskova A, Dinesh DC, Srb P, Boura E, Veverka V, Silhan J. Model of abasic site DNA cross-link repair; from the architecture of NEIL3 DNA binding domains to the X-structure model. Nucleic Acids Res. 2022 Oct 14;50(18):10436-10448. doi: 10.1093/nar/gkac793. PMID:36155818 doi:http://dx.doi.org/10.1093/nar/gkac793

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/7z5a"

Categories: Large Structures | Mus musculus | Synthetic construct | Huskova A | Silhan J

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7z5a is ON HOLD
+==Crystal structure of the trapped complex of mouse Endonuclease VIII-LIKE 3 (mNEIL3) and hairpin DNA with 5'overhang==
+<StructureSection load='7z5a' size='340' side='right'caption='[[7z5a]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7z5a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=7Z5A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z5A FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PED:PENTANE-3,4-DIOL-5-PHOSPHATE'>PED</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=7z5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z5a OCA], [https://pdbe.org/7z5a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z5a RCSB], [https://www.ebi.ac.uk/pdbsum/7z5a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z5a ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NEIL3_MOUSE NEIL3_MOUSE] DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues. Seems to be an important facilitator of cell proliferation in certain populations, for example neural stem/progenitor cells and tumor cells, suggesting a role in replication-associated DNA repair.<ref>PMID:20185759</ref> <ref>PMID:22065741</ref> <ref>PMID:22569481</ref> <ref>PMID:22959434</ref> <ref>PMID:23305905</ref> <ref>PMID:23313161</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Covalent DNA interstrand crosslinks are toxic DNA damage lesions that block the replication machinery that can cause a genomic instability. Ubiquitous abasic DNA sites are particularly susceptible to spontaneous cross-linking with a base from the opposite DNA strand. Detection of a crosslink induces the DNA helicase ubiquitination that recruits NEIL3, a DNA glycosylase responsible for the lesion removal. NEIL3 utilizes several zinc finger domains indispensable for its catalytic NEI domain repairing activity. They recruit NEIL3 to the repair site and bind the single-stranded DNA. However, the molecular mechanism underlying their roles in the repair process is unknown. Here, we report the structure of the tandem zinc-finger GRF domain of NEIL3 and reveal the molecular details of its interaction with DNA. Our biochemical data indicate the preferential binding of the GRF domain to the replication fork. In addition, we obtained a structure for the catalytic NEI domain in complex with the DNA reaction intermediate that allowed us to construct and validate a model for the interplay between the NEI and GRF domains in the recognition of an interstrand cross-link. Our results suggest a mechanism for recognition of the DNA replication X-structure by NEIL3, a key step in the interstrand cross-link repair.
-Authors:
+Model of abasic site DNA cross-link repair; from the architecture of NEIL3 DNA binding domains to the X-structure model.,Huskova A, Dinesh DC, Srb P, Boura E, Veverka V, Silhan J Nucleic Acids Res. 2022 Oct 14;50(18):10436-10448. doi: 10.1093/nar/gkac793. PMID:36155818<ref>PMID:36155818</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7z5a" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Synthetic construct]]
+[[Category: Huskova A]]
+[[Category: Silhan J]]

7z5a

From Proteopedia

Revision as of 19:25, 19 October 2022

Crystal structure of the trapped complex of mouse Endonuclease VIII-LIKE 3 (mNEIL3) and hairpin DNA with 5'overhang

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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