7tqp - Revision history

OCA at 17:07, 18 October 2023

2023-10-18T17:07:11Z

←Older revision		Revision as of 17:07, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7tqp]] is a 1 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=7TQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQP FirstGlance]. <br>		<table><tr><td colspan='2'>[[7tqp]] is a 1 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=7TQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.95Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7tqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqp OCA], [https://pdbe.org/7tqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqp RCSB], [https://www.ebi.ac.uk/pdbsum/7tqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqp ProSAT]</span></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=7tqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqp OCA], [https://pdbe.org/7tqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqp RCSB], [https://www.ebi.ac.uk/pdbsum/7tqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN]] Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations;Familial Chilblain lupus;Systemic lupus erythematosus;Aicardi-Goutieres syndrome. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. Enhanced immune sensing of oxidized DNA may be involved in the phototoxicity experienced by SLE patients. Exposure to UV-light produces DNA oxidative damage. Oxidized DNA being a poor TREX1 substrate, it accumulates in skin, leading to enhanced auto-immune reactivity and eventually skin lesions (PubMed:23993650).<ref>PMID:23993650</ref> The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.	+	[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN] Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations;Familial Chilblain lupus;Systemic lupus erythematosus;Aicardi-Goutieres syndrome. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. Enhanced immune sensing of oxidized DNA may be involved in the phototoxicity experienced by SLE patients. Exposure to UV-light produces DNA oxidative damage. Oxidized DNA being a poor TREX1 substrate, it accumulates in skin, leading to enhanced auto-immune reactivity and eventually skin lesions (PubMed:23993650).<ref>PMID:23993650</ref> The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN]] Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:10393201, PubMed:17293595). Prevents cell-intrinsic initiation of autoimmunity (PubMed:10391904, PubMed:10393201, PubMed:17293595). Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements (PubMed:10391904, PubMed:10393201, PubMed:17293595). Plays a key role in degradation of DNA fragments at cytosolic micronuclei arising from genome instability: its association with the endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei, leading to micronuclear DNA degradation (PubMed:33476576). Micronuclear DNA degradation is required to limit CGAS activation and subsequent inflammation (PubMed:33476576). Unless degraded, these DNA fragments accumulate in the cytosol and activate the cGAS-STING innate immune signaling, leading to the production of type I interferon (PubMed:33476576). Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates (PubMed:18045533). Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light (PubMed:23993650). During GZMA-mediated cell death, contributes to DNA damage in concert with NME1 (PubMed:16818237). NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair (PubMed:16818237).<ref>PMID:10391904</ref> <ref>PMID:10393201</ref> <ref>PMID:16818237</ref> <ref>PMID:17293595</ref> <ref>PMID:18045533</ref> <ref>PMID:23993650</ref> <ref>PMID:33476576</ref>	+	[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN] Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:10393201, PubMed:17293595). Prevents cell-intrinsic initiation of autoimmunity (PubMed:10391904, PubMed:10393201, PubMed:17293595). Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements (PubMed:10391904, PubMed:10393201, PubMed:17293595). Plays a key role in degradation of DNA fragments at cytosolic micronuclei arising from genome instability: its association with the endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei, leading to micronuclear DNA degradation (PubMed:33476576). Micronuclear DNA degradation is required to limit CGAS activation and subsequent inflammation (PubMed:33476576). Unless degraded, these DNA fragments accumulate in the cytosol and activate the cGAS-STING innate immune signaling, leading to the production of type I interferon (PubMed:33476576). Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates (PubMed:18045533). Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light (PubMed:23993650). During GZMA-mediated cell death, contributes to DNA damage in concert with NME1 (PubMed:16818237). NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair (PubMed:16818237).<ref>PMID:10391904</ref> <ref>PMID:10393201</ref> <ref>PMID:16818237</ref> <ref>PMID:17293595</ref> <ref>PMID:18045533</ref> <ref>PMID:23993650</ref> <ref>PMID:33476576</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7tqp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7tqp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Exonuclease 3D structures\|Exonuclease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 03:18, 8 September 2022

2022-09-08T03:18:20Z

←Older revision		Revision as of 03:18, 8 September 2022
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	==Structure of human TREX1==		==Structure of human TREX1==
-	<StructureSection load='7tqp' size='340' side='right'caption='[[7tqp]]' scene=''>	+	<StructureSection load='7tqp' size='340' side='right'caption='[[7tqp]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7tqp]] is a 1 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=7TQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQP FirstGlance]. <br>
-	</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=7tqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqp OCA], [https://pdbe.org/7tqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqp RCSB], [https://www.ebi.ac.uk/pdbsum/7tqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqp ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7tqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqp OCA], [https://pdbe.org/7tqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqp RCSB], [https://www.ebi.ac.uk/pdbsum/7tqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqp ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN]] Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations;Familial Chilblain lupus;Systemic lupus erythematosus;Aicardi-Goutieres syndrome. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. Enhanced immune sensing of oxidized DNA may be involved in the phototoxicity experienced by SLE patients. Exposure to UV-light produces DNA oxidative damage. Oxidized DNA being a poor TREX1 substrate, it accumulates in skin, leading to enhanced auto-immune reactivity and eventually skin lesions (PubMed:23993650).<ref>PMID:23993650</ref> The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN]] Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:10393201, PubMed:17293595). Prevents cell-intrinsic initiation of autoimmunity (PubMed:10391904, PubMed:10393201, PubMed:17293595). Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements (PubMed:10391904, PubMed:10393201, PubMed:17293595). Plays a key role in degradation of DNA fragments at cytosolic micronuclei arising from genome instability: its association with the endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei, leading to micronuclear DNA degradation (PubMed:33476576). Micronuclear DNA degradation is required to limit CGAS activation and subsequent inflammation (PubMed:33476576). Unless degraded, these DNA fragments accumulate in the cytosol and activate the cGAS-STING innate immune signaling, leading to the production of type I interferon (PubMed:33476576). Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates (PubMed:18045533). Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light (PubMed:23993650). During GZMA-mediated cell death, contributes to DNA damage in concert with NME1 (PubMed:16818237). NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair (PubMed:16818237).<ref>PMID:10391904</ref> <ref>PMID:10393201</ref> <ref>PMID:16818237</ref> <ref>PMID:17293595</ref> <ref>PMID:18045533</ref> <ref>PMID:23993650</ref> <ref>PMID:33476576</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	TREX1 is a cytosolic DNA nuclease essential for regulation of cGAS-STING immune signaling. Existing structures of mouse TREX1 establish a mechanism of DNA degradation and provide a key model to explain autoimmune disease, but these structures incompletely explain human disease-associated mutations and have limited ability to guide development of small-molecule therapeutics. Here we determine crystal structures of human TREX1 in apo and DNA-bound conformations that provide high-resolution detail of all human-specific features. A 1.25 A structure of human TREX1 establishes a complete model of solvation of the exonuclease active site and a 2.2 A structure of the human TREX1-DNA complex enables identification of specific substitutions involved in DNA recognition. We map each TREX1 mutation associated with autoimmune disease and establish distinct categories of substitutions predicted to impact enzymatic function, protein stability, and interaction with cGAS-DNA liquid droplets. Our results explain how human-specific substitutions regulate TREX1 function and provide a foundation for structure-guided design of TREX1 therapeutics.
		+
		+	Structural basis of human TREX1 DNA degradation and autoimmune disease.,Zhou W, Richmond-Buccola D, Wang Q, Kranzusch PJ Nat Commun. 2022 Jul 25;13(1):4277. doi: 10.1038/s41467-022-32055-z. PMID:35879334<ref>PMID:35879334</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7tqp" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kranzusch PJ]]		[[Category: Kranzusch PJ]]
	[[Category: Richmond-Buccola D]]		[[Category: Richmond-Buccola D]]
	[[Category: Zhou W]]		[[Category: Zhou W]]

OCA at 04:53, 3 August 2022

2022-08-03T04:53:39Z

←Older revision		Revision as of 04:53, 3 August 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7tqp is ~~ON HOLD until Paper Publication~~	+	==Structure of human TREX1==
-		+	<StructureSection load='7tqp' size='340' side='right'caption='[[7tqp]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQP FirstGlance]. <br>
-	~~Description~~:	+	</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=7tqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqp OCA], [https://pdbe.org/7tqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqp RCSB], [https://www.ebi.ac.uk/pdbsum/7tqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqp ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Kranzusch PJ]]
		+	[[Category: Richmond-Buccola D]]
		+	[[Category: Zhou W]]

OCA at 09:08, 16 February 2022

2022-02-16T09:08:03Z

←Older revision		Revision as of 09:08, 16 February 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7tqp is ON HOLD	+	The entry 7tqp is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7tqp" [edit=sysop:move=sysop]

2022-02-02T05:43:11Z

Protected "7tqp" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:43, 2 February 2022

OCA: New page: '''Unreleased structure''' The entry 7tqp is ON HOLD Authors: Description: Category: Unreleased Structures

2022-02-02T05:43:10Z

New page: '''Unreleased structure''' The entry 7tqp is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7tqp is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]