6w10: Difference between revisions
m Protected "6w10" [edit=sysop:move=sysop] |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Structure of mouse TREX1 with E198K disease-associated mutation== | |||
<StructureSection load='6w10' size='340' side='right'caption='[[6w10]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8000338Å</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> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:33606975</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6w10" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Exonuclease 3D structures|Exonuclease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Kranzusch PJ]] | |||
[[Category: Maciejowski J]] | |||
[[Category: Mohr L]] | |||
[[Category: Zhou W]] | |||
Latest revision as of 17:14, 18 October 2023
Structure of mouse TREX1 with E198K disease-associated mutationStructure of mouse TREX1 with E198K disease-associated mutation
Structural highlights
FunctionTREX1_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 PubMedCyclic 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. See AlsoReferences
|
| ||||||||||||||||