9k6i

From Proteopedia

(Difference between revisions)

Current revision

Structure of full-length human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid

Structural highlights

9k6i is a 5 chain structure with sequence from Homo sapiens and Trichoplusia ni. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dombroski BA, Feng Q, Mathias SL, Sassaman DM, Scott AF, Kazazian HH Jr, Boeke JD. An in vivo assay for the reverse transcriptase of human retrotransposon L1 in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Jul;14(7):4485-92. doi: 10.1128/mcb.14.7.4485-4492.1994. PMID:7516468 doi:http://dx.doi.org/10.1128/mcb.14.7.4485-4492.1994
↑ Feng Q, Moran JV, Kazazian HH Jr, Boeke JD. Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell. 1996 Nov 29;87(5):905-16. doi: 10.1016/s0092-8674(00)81997-2. PMID:8945517 doi:http://dx.doi.org/10.1016/s0092-8674(00)81997-2
↑ Sassaman DM, Dombroski BA, Moran JV, Kimberland ML, Naas TP, DeBerardinis RJ, Gabriel A, Swergold GD, Kazazian HH Jr. Many human L1 elements are capable of retrotransposition. Nat Genet. 1997 May;16(1):37-43. PMID:9140393 doi:http://dx.doi.org/10.1038/ng0597-37
↑ Jin W, Yu C, Zhang Y, Cao C, Xia T, Song G, Cai Z, Xue Y, Zhu B, Xu RM. Mechanism of DNA targeting by human LINE-1. Science. 2025 Oct 9;390(6769):eadu3433. PMID:41066570 doi:10.1126/science.adu3433

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9k6i"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9k6i is ON HOLD  until Paper Publication
+==Structure of full-length human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid==
+<StructureSection load='9k6i' size='340' side='right'caption='[[9k6i]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9k6i]] 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=9K6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9K6I 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]] 3.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=9k6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9k6i OCA], [https://pdbe.org/9k6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9k6i RCSB], [https://www.ebi.ac.uk/pdbsum/9k6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9k6i 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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9k6i" 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]]

9k6i

From Proteopedia

Current revision

Structure of full-length human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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