9k6h: Difference between revisions
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==Structure of human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid bound to dNTP and Mn2+== | |||
<StructureSection load='9k6h' size='340' side='right'caption='[[9k6h]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9k6h]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Trichoplusia_ni Trichoplusia ni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9K6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9K6H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9k6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9k6h OCA], [https://pdbe.org/9k6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9k6h RCSB], [https://www.ebi.ac.uk/pdbsum/9k6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9k6h ProSAT]</span></td></tr> | |||
</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 (LINE-1 or L1), the only autonomously active retrotransposon in humans today, constitutes a large proportion of the genome and continues to evolve the genome and impact fundamental biological processes. L1 retrotransposition critically depends on its endonuclease and reverse transcriptase subunit open reading frame 2 protein (ORF2p), which targets genomic loci and nicks DNA using an evolutionarily distinct yet not fully understood mechanism. Our structural and biochemical analyses revealed that ORF2p is a structure-dependent endonuclease. It binds a double-stranded DNA region upstream of the nicking site and recognizes a downstream forked or flap structure for efficient DNA nicking. This discovery suggests that L1 mobilization piggybacks on chromosomal processes with noncanonical DNA structure intermediates. | |||
Mechanism of DNA targeting by human LINE-1.,Jin W, Yu C, Zhang Y, Cao C, Xia T, Song G, Cai Z, Xue Y, Zhu B, Xu RM Science. 2025 Oct 9;390(6769):eadu3433. doi: 10.1126/science.adu3433. Epub 2025 , Oct 9. PMID:41066570<ref>PMID:41066570</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9k6h" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Trichoplusia ni]] | |||
[[Category: Jin W]] | |||
[[Category: Xu RM]] | |||
[[Category: Yu C]] | |||
