6sxa

From Proteopedia

(Difference between revisions)

Current revision

XPF-ERCC1 Cryo-EM Structure, Apo-form

Structural highlights

6sxa is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

XPF_HUMAN Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:278760; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.^[1] ^[2] ^[3] Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:610965. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.^[4]

Function

XPF_HUMAN Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.^[5]

Publication Abstract from PubMed

The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated by DNA junction substrates is not currently understood. Here we report cryo-electron microscopy structures of both DNA-free and DNA-bound human XPF-ERCC1. DNA-free XPF-ERCC1 adopts an auto-inhibited conformation in which the XPF helical domain masks the ERCC1 (HhH)2 domain and restricts access to the XPF catalytic site. DNA junction engagement releases the ERCC1 (HhH)2 domain to couple with the XPF-ERCC1 nuclease/nuclease-like domains. Structure-function data indicate xeroderma pigmentosum patient mutations frequently compromise the structural integrity of XPF-ERCC1. Fanconi anaemia patient mutations in XPF often display substantial in-vitro activity but are resistant to activation by ICLR recruitment factor SLX4. Our data provide insights into XPF-ERCC1 architecture and catalytic activation.

Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.,Jones M, Beuron F, Borg A, Nans A, Earl CP, Briggs DC, Snijders AP, Bowles M, Morris EP, Linch M, McDonald NQ Nat Commun. 2020 Feb 28;11(1):1120. doi: 10.1038/s41467-020-14856-2. PMID:32111838^[6]

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

References

↑ Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, Moggs JG, Carter KC, Shell BK, Evans E, de Jong MC, Rademakers S, de Rooij J, Jaspers NG, Hoeijmakers JH, Wood RD. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell. 1996 Sep 6;86(5):811-22. PMID:8797827
↑ Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms. Hum Mol Genet. 1998 Jun;7(6):969-74. PMID:9580660
↑ Sijbers AM, van Voorst Vader PC, Snoek JW, Raams A, Jaspers NG, Kleijer WJ. Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease. J Invest Dermatol. 1998 May;110(5):832-6. PMID:9579555 doi:10.1046/j.1523-1747.1998.00171.x
↑ Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, Odijk H, Oostendorp R, Ahmad A, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GT, Meinecke P, Kleijer WJ, Vijg J, Jaspers NG, Hoeijmakers JH. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature. 2006 Dec 21;444(7122):1038-43. PMID:17183314 doi:nature05456
↑ Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW. Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009 Jul 10;138(1):63-77. PMID:19596235 doi:S0092-8674(09)00777-6
↑ Jones M, Beuron F, Borg A, Nans A, Earl CP, Briggs DC, Snijders AP, Bowles M, Morris EP, Linch M, McDonald NQ. Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation. Nat Commun. 2020 Feb 28;11(1):1120. doi: 10.1038/s41467-020-14856-2. PMID:32111838 doi:http://dx.doi.org/10.1038/s41467-020-14856-2

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/6sxa"

Categories: Homo sapiens | Large Structures | Briggs DC | Jones ML | McDonald NQ

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6sxa is ON HOLD
+==XPF-ERCC1 Cryo-EM Structure, Apo-form==
+<StructureSection load='6sxa' size='340' side='right'caption='[[6sxa]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6sxa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SXA FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6&#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=6sxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sxa OCA], [https://pdbe.org/6sxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sxa RCSB], [https://www.ebi.ac.uk/pdbsum/6sxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sxa ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/XPF_HUMAN XPF_HUMAN] Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:[https://omim.org/entry/278760 278760]; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.<ref>PMID:8797827</ref> <ref>PMID:9580660</ref> <ref>PMID:9579555</ref>   Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:[https://omim.org/entry/610965 610965]. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.<ref>PMID:17183314</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/XPF_HUMAN XPF_HUMAN] Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.<ref>PMID:19596235</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated by DNA junction substrates is not currently understood. Here we report cryo-electron microscopy structures of both DNA-free and DNA-bound human XPF-ERCC1. DNA-free XPF-ERCC1 adopts an auto-inhibited conformation in which the XPF helical domain masks the ERCC1 (HhH)2 domain and restricts access to the XPF catalytic site. DNA junction engagement releases the ERCC1 (HhH)2 domain to couple with the XPF-ERCC1 nuclease/nuclease-like domains. Structure-function data indicate xeroderma pigmentosum patient mutations frequently compromise the structural integrity of XPF-ERCC1. Fanconi anaemia patient mutations in XPF often display substantial in-vitro activity but are resistant to activation by ICLR recruitment factor SLX4. Our data provide insights into XPF-ERCC1 architecture and catalytic activation.
-Authors:
+Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.,Jones M, Beuron F, Borg A, Nans A, Earl CP, Briggs DC, Snijders AP, Bowles M, Morris EP, Linch M, McDonald NQ Nat Commun. 2020 Feb 28;11(1):1120. doi: 10.1038/s41467-020-14856-2. PMID:32111838<ref>PMID:32111838</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 6sxa" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Endonuclease 3D structures|Endonuclease 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Briggs DC]]
+[[Category: Jones ML]]
+[[Category: McDonald NQ]]

6sxa

From Proteopedia

Current revision

XPF-ERCC1 Cryo-EM Structure, Apo-form

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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