9HDO

The Human LINE-1 ORF2p target-primed reverse transcription complex

9HDO の概要

• エントリーDOI: 10.2210/pdb9hdo/pdb
• 関連するPDBエントリー: 9HDP 9HDQ 9HDR
• EMDBエントリー: 52070 52071 52072 52073
• 分子名称: LINE-1 retrotransposable element ORF2 protein, 2',3'-DIDEOXY-THYMIDINE-5'-TRIPHOSPHATE, Target DNA strand 1, ... (10 entities in total)
• 機能のキーワード: line-1, l1, orf2p, reverse transcriptase, endonuclease, dna, rna, rna binding protein
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 252688.01

構造登録者

Ghanim, G.E.,Hu, H.,Nguyen, T.H.D. (登録日: 2024-11-12, 公開日: 2025-03-12, 最終更新日: 2025-05-07)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.3 Å)