9K6H
Structure of human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid bound to dNTP and Mn2+
Summary for 9K6H
| Entry DOI | 10.2210/pdb9k6h/pdb |
| EMDB information | 62127 |
| Descriptor | LINE-1 retrotransposable element ORF2 protein, Genomic DNA (top strand), Genomic DNA (bottom strand), ... (8 entities in total) |
| Functional Keywords | endonuclease, reverse transcriptase, gene regulation |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 166113.15 |
| Authors | |
| Primary citation | Jin, W.,Yu, C.,Zhang, Y.,Cao, C.,Xia, T.,Song, G.,Cai, Z.,Xue, Y.,Zhu, B.,Xu, R.M. Mechanism of DNA targeting by human LINE-1. Science, 390:eadu3433-eadu3433, 2025 Cited by PubMed Abstract: 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. PubMed: 41066570DOI: 10.1126/science.adu3433 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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