Human LINE-1 ORF2p target-primed reverse transcription complex with EN domain resolved
マップデータ
LINE-1 ORF2p TPRT Complex EN Resolved Sharpened Map
試料
複合体: Human LINE-1 ORF2p target-primed reverse transcription complex with EN domain resolved
複合体: ORF2p
タンパク質・ペプチド: LINE-1 retrotransposable element ORF2 protein
複合体: Target DNA
DNA: Target DNA strand 1
DNA: Target DNA strand 2
DNA: Target DNA strand 3
DNA: Target DNA strand 4
RNA: Template P(A)30 RNA
DNA: Unassigned Nucleic Acid
リガンド: MAGNESIUM ION
リガンド: ZINC ION
リガンド: 2',3'-DIDEOXY-THYMIDINE-5'-TRIPHOSPHATE
キーワード
LINE-1 / L1 / ORF2p / Reverse transcriptase / endonuclease / DNA / RNA / RNA BINDING PROTEIN
機能・相同性
機能・相同性情報
nucleic acid metabolic process / retrotransposition / SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / SUMOylation of transcription factors / SUMOylation of transcription cofactors / Postmitotic nuclear pore complex (NPC) reformation / septin ring ...nucleic acid metabolic process / retrotransposition / SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / SUMOylation of transcription factors / SUMOylation of transcription cofactors / Postmitotic nuclear pore complex (NPC) reformation / septin ring / SUMOylation of DNA damage response and repair proteins / type II site-specific deoxyribonuclease activity / Transcriptional and post-translational regulation of MITF-M expression and activity / SUMOylation of DNA replication proteins / SUMOylation of SUMOylation proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エンドデオキシリボヌクレアーゼ / SUMOylation of RNA binding proteins / SUMOylation of chromatin organization proteins / detection of maltose stimulus / maltose transport complex / carbohydrate transport / ubiquitin-like protein ligase binding / protein sumoylation / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / RNA-directed DNA polymerase activity / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / ATP-binding cassette (ABC) transporter complex / condensed nuclear chromosome / cell chemotaxis / RNA-directed DNA polymerase / protein tag activity / telomerase activity / outer membrane-bounded periplasmic space / DNA recombination / periplasmic space / DNA damage response / RNA binding / metal ion binding / identical protein binding / nucleus / membrane 類似検索 - 分子機能
Rad60/SUMO-like domain / Ubiquitin-2 like Rad60 SUMO-like / Endonuclease/exonuclease/phosphatase / Endonuclease/Exonuclease/phosphatase family / Endonuclease/exonuclease/phosphatase superfamily / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein ...Rad60/SUMO-like domain / Ubiquitin-2 like Rad60 SUMO-like / Endonuclease/exonuclease/phosphatase / Endonuclease/Exonuclease/phosphatase family / Endonuclease/exonuclease/phosphatase superfamily / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Reverse transcriptase domain / Reverse transcriptase (RNA-dependent DNA polymerase) / Reverse transcriptase (RT) catalytic domain profile. / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / DNA/RNA polymerase superfamily 類似検索 - ドメイン・相同性
LINE-1 retrotransposable element ORF2 protein / Maltose/maltodextrin-binding periplasmic protein / Ubiquitin-like protein SMT3 類似検索 - 構成要素
ジャーナル: Science / 年: 2025 タイトル: Structural mechanism of LINE-1 target-primed reverse transcription. 著者: George E Ghanim / Hongmiao Hu / Jerome Boulanger / Thi Hoang Duong Nguyen / 要旨: Long interspersed element-1 (LINE-1) retrotransposons are the only active autonomous transposable elements in humans. They propagate by reverse transcribing their messenger RNA into new genomic ...Long interspersed element-1 (LINE-1) retrotransposons are the only active autonomous transposable elements in humans. They propagate by reverse transcribing their messenger RNA into new genomic locations by a process called target-primed reverse transcription (TPRT). In this work, we present four cryo-electron microscopy structures of the human LINE-1 TPRT complex, revealing the conformational dynamics of open reading frame 2 protein (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 proliferating cell nuclear antigen (PCNA) and cytoplasmic poly(A)-binding protein 1 (PABPC1)-on ORF2p. Together with our structural data, this suggests a mechanism by which these factors regulate retrotransposition and supports a model for TPRT that accounts for retrotransposition outcomes observed in cells.
全体 : Human LINE-1 ORF2p target-primed reverse transcription complex wi...
全体
名称: Human LINE-1 ORF2p target-primed reverse transcription complex with EN domain resolved
要素
複合体: Human LINE-1 ORF2p target-primed reverse transcription complex with EN domain resolved
複合体: ORF2p
タンパク質・ペプチド: LINE-1 retrotransposable element ORF2 protein
複合体: Target DNA
DNA: Target DNA strand 1
DNA: Target DNA strand 2
DNA: Target DNA strand 3
DNA: Target DNA strand 4
RNA: Template P(A)30 RNA
DNA: Unassigned Nucleic Acid
リガンド: MAGNESIUM ION
リガンド: ZINC ION
リガンド: 2',3'-DIDEOXY-THYMIDINE-5'-TRIPHOSPHATE
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超分子 #1: Human LINE-1 ORF2p target-primed reverse transcription complex wi...
超分子
名称: Human LINE-1 ORF2p target-primed reverse transcription complex with EN domain resolved タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#7 詳細: The human LINE-1 retrotransposon mobilizes using the encoded ORF2p protein by a mechanism called target-primed reverse transcription.
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 5)
最終 角度割当
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 5)
最終 3次元分類
クラス数: 6 / ソフトウェア - 名称: RELION (ver. 5)
FSC曲線 (解像度の算出)
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原子モデル構築 1
初期モデル
Chain - Chain ID: A / Chain - Residue range: 1-1275 / Chain - Source name: AlphaFold / Chain - Initial model type: in silico model 詳細: Initial model was an alphaFold 2 prediction and was rebuilt into the density.
得られたモデル
PDB-9hdr: Human LINE-1 ORF2p target-primed reverse transcription complex with EN domain resolved