9l88: Difference between revisions
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The entry | ==Structure of human TREX1-DNA complex with K66R disease-associated mutation== | ||
<StructureSection load='9l88' size='340' side='right'caption='[[9l88]], [[Resolution|resolution]] 2.62Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9l88]] is a 8 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=9L88 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9L88 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.62Å</td></tr> | |||
[[Category: | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LI:LITHIUM+ION'>LI</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=9l88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9l88 OCA], [https://pdbe.org/9l88 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9l88 RCSB], [https://www.ebi.ac.uk/pdbsum/9l88 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9l88 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/TREX1_HUMAN TREX1_HUMAN] Familial Chilblain lupus;Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations;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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Lin C]] | |||
[[Category: Wang L]] | |||
[[Category: Zhou W]] | |||
[[Category: Zhu J]] | |||
Latest revision as of 08:09, 29 April 2026
Structure of human TREX1-DNA complex with K66R disease-associated mutation
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