7n94
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==LINE-1 endonuclease domain complex with DNA== |
| - | <StructureSection load='7n94' size='340' side='right'caption='[[7n94]]' scene=''> | + | <StructureSection load='7n94' size='340' side='right'caption='[[7n94]], [[Resolution|resolution]] 2.85Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7n94]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N94 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N94 FirstGlance]. <br> |
| - | </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=7n94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n94 OCA], [https://pdbe.org/7n94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n94 RCSB], [https://www.ebi.ac.uk/pdbsum/7n94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n94 ProSAT]</span></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]] 2.85Å</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=7n94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n94 OCA], [https://pdbe.org/7n94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n94 RCSB], [https://www.ebi.ac.uk/pdbsum/7n94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n94 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LORF2_HUMAN LORF2_HUMAN] Has a reverse transcriptase activity required for target-primed reverse transcription of the LINE-1 element mRNA, a crucial step in LINE-1 retrotransposition. Has also an endonuclease activity that allows the introduction of nicks in the chromosomal target DNA. Cleaves DNA in AT-rich regions between a 5' stretch of purines and a 3' stretch of pyrimidines, corresponding to sites of LINE-1 integration in the genome.<ref>PMID:7516468</ref> <ref>PMID:8945517</ref> <ref>PMID:9140393</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Long interspersed nuclear element-1 (L1) is an autonomous non-LTR retrotransposon comprising approximately 20% of the human genome. L1 self-propagation causes genomic instability and is strongly associated with aging, cancer and other diseases. The endonuclease domain of L1's ORFp2 protein (L1-EN) initiates de novo L1 integration by nicking the consensus sequence 5'-TTTTT/AA-3'. In contrast, related nucleases including structurally conserved apurinic/apyrimidinic endonuclease 1 (APE1) are non-sequence specific. To investigate mechanisms underlying sequence recognition and catalysis by L1-EN, we solved crystal structures of L1-EN complexed with DNA substrates. This showed that conformational properties of the preferred sequence drive L1-EN's sequence-specificity and catalysis. Unlike APE1, L1-EN does not bend the DNA helix, but rather causes 'compression' near the cleavage site. This provides multiple advantages for L1-EN's role in retrotransposition including facilitating use of the nicked poly-T DNA strand as a primer for reverse transcription. We also observed two alternative conformations of the scissile bond phosphate, which allowed us to model distinct conformations for a nucleophilic attack and a transition state that are likely applicable to the entire family of nucleases. This work adds to our mechanistic understanding of L1-EN and related nucleases and should facilitate development of L1-EN inhibitors as potential anticancer and antiaging therapeutics. | ||
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| + | Structural dissection of sequence recognition and catalytic mechanism of human LINE-1 endonuclease.,Miller I, Totrov M, Korotchkina L, Kazyulkin DN, Gudkov AV, Korolev S Nucleic Acids Res. 2021 Sep 23. pii: 6374484. doi: 10.1093/nar/gkab826. PMID:34554261<ref>PMID:34554261</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7n94" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Korolev S]] |
| + | [[Category: Miller I]] | ||
Current revision
LINE-1 endonuclease domain complex with DNA
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