6w10

From Proteopedia

(Difference between revisions)

Current revision

Structure of mouse TREX1 with E198K disease-associated mutation

Structural highlights

6w10 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8000338Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TREX1_MOUSE Exonuclease with a preference for double stranded DNA with mismatched 3' termini. May play a role in DNA repair.^[1] ^[2]

Publication Abstract from PubMed

Cyclic GMP-AMP synthase (cGAS) recognition of cytosolic DNA is critical for the immune response to cancer and pathogen infection. Here, we discover that cGAS-DNA phase separation is required to resist negative regulation and allow efficient sensing of immunostimulatory DNA. We map the molecular determinants of cGAS condensate formation and demonstrate that phase separation functions to limit activity of the cytosolic exonuclease TREX1. Mechanistically, phase separation forms a selective environment that suppresses TREX1 catalytic function and restricts DNA degradation to an outer shell at the droplet periphery. We identify a TREX1 mutation associated with the severe autoimmune disease Aicardi-Goutieres syndrome that increases penetration of TREX1 into the repressive droplet interior and specifically impairs degradation of phase-separated DNA. Our results define a critical function of cGAS-DNA phase separation and reveal a molecular mechanism that balances cytosolic DNA degradation and innate immune activation.

cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing.,Zhou W, Mohr L, Maciejowski J, Kranzusch PJ Mol Cell. 2021 Feb 18;81(4):739-755.e7. doi: 10.1016/j.molcel.2021.01.024. PMID:33606975^[3]

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

References

↑ Mazur DJ, Perrino FW. Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases. J Biol Chem. 1999 Jul 9;274(28):19655-60. PMID:10391904
↑ Mazur DJ, Perrino FW. Excision of 3' termini by the Trex1 and TREX2 3'-->5' exonucleases. Characterization of the recombinant proteins. J Biol Chem. 2001 May 18;276(20):17022-9. Epub 2001 Mar 6. PMID:11279105 doi:http://dx.doi.org/10.1074/jbc.M100623200
↑ Zhou W, Mohr L, Maciejowski J, Kranzusch PJ. cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing. Mol Cell. 2021 Feb 18;81(4):739-755.e7. doi: 10.1016/j.molcel.2021.01.024. PMID:33606975 doi:http://dx.doi.org/10.1016/j.molcel.2021.01.024

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/6w10"

@@ Line 3: / Line 3: @@
 <StructureSection load='6w10' size='340' side='right'caption='[[6w10]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6w10]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W10 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6w10]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W10 FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trex1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 1.8000338&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Exodeoxyribonuclease_III Exodeoxyribonuclease III], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.11.2 3.1.11.2] </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=6w10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w10 OCA], [https://pdbe.org/6w10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w10 RCSB], [https://www.ebi.ac.uk/pdbsum/6w10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w10 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/TREX1_MOUSE TREX1_MOUSE]] Exonuclease with a preference for double stranded DNA with mismatched 3' termini. May play a role in DNA repair.<ref>PMID:10391904</ref> <ref>PMID:11279105</ref>
+[https://www.uniprot.org/uniprot/TREX1_MOUSE TREX1_MOUSE] Exonuclease with a preference for double stranded DNA with mismatched 3' termini. May play a role in DNA repair.<ref>PMID:10391904</ref> <ref>PMID:11279105</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 18: @@
 </div>
 <div class="pdbe-citations 6w10" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Exonuclease 3D structures|Exonuclease 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Exodeoxyribonuclease III]]
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Kranzusch, P J]]
+[[Category: Kranzusch PJ]]
-[[Category: Maciejowski, J]]
+[[Category: Maciejowski J]]
-[[Category: Mohr, L]]
+[[Category: Mohr L]]
-[[Category: Zhou, W]]
+[[Category: Zhou W]]
-[[Category: Autoimmunity]]
-[[Category: Dnase]]
-[[Category: Hydrolase]]
-[[Category: Innate immunity]]
-[[Category: Nuclease]]

6w10

From Proteopedia

Current revision

Structure of mouse TREX1 with E198K disease-associated mutation

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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