2oa8

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{{STRUCTURE_2oa8| PDB=2oa8 | SCENE= }}
{{STRUCTURE_2oa8| PDB=2oa8 | SCENE= }}
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'''Crystal Structure of mTREX1 with ssDNA'''
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===Crystal Structure of mTREX1 with ssDNA===
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==Overview==
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The TREX1 enzyme processes DNA ends as the major 3' --&gt; 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.
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{{ABSTRACT_PUBMED_17293595}}
==About this Structure==
==About this Structure==
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[[Category: Poly-proline helix]]
[[Category: Poly-proline helix]]
[[Category: Ssdna complex]]
[[Category: Ssdna complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:30:50 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:32:29 2008''

Revision as of 17:32, 27 July 2008

Image:2oa8.png

Template:STRUCTURE 2oa8

Crystal Structure of mTREX1 with ssDNA

Template:ABSTRACT PUBMED 17293595

About this Structure

2OA8 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

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;282(14):10537-43. Epub 2007 Feb 9. PMID:17293595

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