9HDQ

The Human LINE-1 ORF2p target-primed reverse transcription complex with the fingers domain in an open conformation

Summary for 9HDQ

• Entry DOI: 10.2210/pdb9hdq/pdb
• Related: 9HDO 9HDP 9HDR
• EMDB information: 52070 52071 52072 52073
• Descriptor: LINE-1 retrotransposable element ORF2 protein, Target DNA strand 1, Target DNA strand 2, ... (8 entities in total)
• Functional Keywords: line-1, l1, orf2p, reverse transcriptase, endonuclease, dna, rna, rna binding protein
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 7
• Total formula weight: 252197.53

Authors

Ghanim, G.E.,Hu, H.,Nguyen, T.H.D. (deposition date: 2024-11-12, release date: 2025-03-12, Last modification date: 2025-05-07)

Primary citation

Ghanim, G.E.,Hu, H.,Boulanger, J.,Nguyen, T.H.D.
Structural mechanism of LINE-1 target-primed reverse transcription.
Science, 388:eads8412-eads8412, 2025

PubMed Abstract: Long interspersed element-1 (LINE-1) retrotransposons are the only active autonomous transposable elements in humans. They propagate by reverse transcribing their mRNA into new genomic locations by a process called target-primed reverse transcription (TPRT). Here, we present four cryo-electron microscopy structures of the human LINE-1 TPRT complex, revealing the conformational dynamics of ORF2p and its extensive remodeling of the target DNA for TPRT initiation. We observe nicking of the DNA second strand during reverse transcription of the first strand. Structure prediction identifies high-confidence binding sites for LINE-1-associated factors, namely PCNA and PABPC1, on ORF2p. Together with our structural data, this suggests a mechanism by which these factors regulate retrotransposition and proposes a model for TPRT that accounts for retrotransposition outcomes observed in cells.

PubMed: 40048554
DOI: 10.1126/science.ads8412

Experimental method

ELECTRON MICROSCOPY (2.45 Å)