2ioc: Difference between revisions
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==The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partenring== | ==The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partenring== | ||
<StructureSection load='2ioc' size='340' side='right' caption='[[2ioc]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='2ioc' size='340' side='right'caption='[[2ioc]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2ioc]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2ioc]] 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=2IOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IOC FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D5M:2-DEOXYADENOSINE-5-MONOPHOSPHATE'>D5M</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2ioc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ioc OCA], [https://pdbe.org/2ioc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ioc RCSB], [https://www.ebi.ac.uk/pdbsum/2ioc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ioc ProSAT]</span></td></tr> | |||
< | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/io/2ioc_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/io/2ioc_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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</div> | </div> | ||
<div class="pdbe-citations 2ioc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2ioc" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Exonuclease 3D structures|Exonuclease 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Hollis | [[Category: Hollis T]] | ||
[[Category: Silva | [[Category: De Silva U]] | ||
Latest revision as of 12:12, 6 November 2024
The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partenringThe crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partenring
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] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe TREX1 enzyme processes DNA ends as the major 3' --> 5' exonuclease activity in human cells. Mutations in the TREX1 gene are an underlying cause of the neurological brain disease Aicardi-Goutieres syndrome implicating TREX1 dysfunction in an aberrant immune response. TREX1 action during apoptosis likely prevents autoimmune reaction to DNA that would otherwise persist. To understand the impact of TREX1 mutations identified in patients with Aicardi-Goutieres syndrome on structure and activity we determined the x-ray crystal structure of the dimeric mouse TREX1 protein in substrate and product complexes containing single-stranded DNA and deoxyadenosine monophosphate, respectively. The structures show the specific interactions between the bound nucleotides and the residues lining the binding pocket of the 3' terminal nucleotide within the enzyme active site that account for specificity, and provide the molecular basis for understanding mutations that lead to disease. Three mutant forms of TREX1 protein identified in patients with Aicardi-Goutieres syndrome were prepared and the measured activities show that these specific mutations reduce enzyme activity by 4-35,000-fold. The structure also reveals an 8-amino acid polyproline II helix within the TREX1 enzyme that suggests a mechanism for interactions of this exonuclease with other protein complexes. The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering.,de Silva U, Choudhury S, Bailey SL, Harvey S, Perrino FW, Hollis T J Biol Chem. 2007 Apr 6;282(14):10537-43. Epub 2007 Feb 9. PMID:17293595[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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