EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Modelling POLG mutations in mice unravels a critical role of POLγΒ in regulating phenotypic severity.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 4782, Year 2025
掲載日	2025年5月23日
著者	Samantha Corrà / Alessandro Zuppardo / Sebastian Valenzuela / Louise Jenninger / Raffaele Cerutti / Sirelin Sillamaa / Emily Hoberg / Katarina A S Johansson / Urska Rovsnik / Sara Volta / Pedro Silva-Pinheiro / Hannah Davis / Aleksandra Trifunovic / Michal Minczuk / Claes M Gustafsson / Anu Suomalainen / Massimo Zeviani / Bertil Macao / Xuefeng Zhu / Maria Falkenberg / Carlo Viscomi /
PubMed 要旨	DNA polymerase γ (POLγ), responsible for mitochondrial DNA replication, consists of a catalytic POLγA subunit and two accessory POLγB subunits. Mutations in POLG, which encodes POLγA, lead to ...DNA polymerase γ (POLγ), responsible for mitochondrial DNA replication, consists of a catalytic POLγA subunit and two accessory POLγB subunits. Mutations in POLG, which encodes POLγA, lead to various mitochondrial diseases. We investigated the most common POLG mutations (A467T, W748S, G848S, Y955C) by characterizing human and mouse POLγ variants. Our data reveal that these mutations significantly impair POLγ activities, with mouse variants exhibiting milder defects. Cryogenic electron microscopy highlighted structural differences between human and mouse POLγ, particularly in the POLγB subunit, which may explain the higher activity of mouse POLγ and the reduced severity of mutations in mice. We further generated a panel of mouse models mirroring common human POLG mutations, providing crucial insights into the pathogenesis of POLG-related disorders and establishing robust models for therapeutic development. Our findings emphasize the importance of POLγB in modulating the severity of POLG mutations.
リンク	Nat Commun / PubMed:40404629 / PubMed Central
手法	EM (単粒子)
解像度	2.54 - 3.24 Å
構造データ	51109 9g74 EMDB-51109, PDB-9g74: Mouse mitochondrial DNA polymerase gamma ternary complex in replication conformer 手法: EM (単粒子) / 解像度: 2.75 Å 51110 9g75 EMDB-51110, PDB-9g75: Mouse mitochondrial DNA polymerase gamma ternary complex in intermediate conformer 手法: EM (単粒子) / 解像度: 2.98 Å EMDB-51111: Mouse mitochondrial DNA polymerase gamma ternary complex in error-editing conformer (consensus map) 手法: EM (単粒子) / 解像度: 2.87 Å EMDB-51112: Mouse mitochondrial DNA polymerase gamma ternary complex in error-editing conformer (Local refinement map of subunit A and DNA) 手法: EM (単粒子) / 解像度: 2.77 Å EMDB-51113: Mouse mitochondrial DNA polymerase gamma ternary complex in error-editing conformer (local refinement of subunit B) 手法: EM (単粒子) / 解像度: 2.7 Å 51114 9g77 EMDB-51114: Mouse mitochondrial DNA polymerase gamma ternary complex in error-editing conformer PDB-9g77: Mouse mitochondrial DNA polymerase gamma ternary complex in error-editing conformer (composite) 手法: EM (単粒子) / 解像度: 2.87 Å 52815 9ibx EMDB-52815, PDB-9ibx: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in replication conformer 手法: EM (単粒子) / 解像度: 2.54 Å EMDB-52816: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in human-like error-editing conformer (consensus map) 手法: EM (単粒子) / 解像度: 3.08 Å EMDB-52817: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in human-like error-editing conformer (local refinement map of subunit A and DNA) 手法: EM (単粒子) / 解像度: 3.02 Å EMDB-52818: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in human-like error-editing conformer (local refinement map of subunit B) 手法: EM (単粒子) / 解像度: 2.94 Å 52819 9ibz EMDB-52819, PDB-9ibz: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in human-like error-editing conformer (composite) 手法: EM (単粒子) / 解像度: 3.08 Å EMDB-52820: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in mouse-like error-editing conformer (consensus map) 手法: EM (単粒子) / 解像度: 3.24 Å EMDB-52821: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in mouse-like error-editing conformer (local refinement map of subunit A and DNA) 手法: EM (単粒子) / 解像度: 3.09 Å EMDB-52822: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in mouse-like error-editing conformer (local refinement map of subunit B) 手法: EM (単粒子) / 解像度: 3.19 Å 52823 9ic0 EMDB-52823, PDB-9ic0: Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in mouse-like error-editing conformer (composite) 手法: EM (単粒子) / 解像度: 3.24 Å 52824 9ic1 EMDB-52824, PDB-9ic1: Chimeric mitochondrial DNA polymerase gamma ternary complex (hAmB) in replication conformer 手法: EM (単粒子) / 解像度: 2.73 Å EMDB-52825: Chimeric mitochondrial DNA polymerase gamma ternary complex (hAmB) in mouse-like error-editing conformer (consensus map) 手法: EM (単粒子) / 解像度: 2.96 Å EMDB-52826: Chimeric mitochondrial DNA polymerase gamma ternary complex (hAmB) in mouse-like error-editing conformer (local refinement map of subunit A and DNA) 手法: EM (単粒子) / 解像度: 2.87 Å EMDB-52827: Chimeric mitochondrial DNA polymerase gamma ternary complex (hAmB) in mouse-like error-editing conformer (local refinement map of subunit B) 手法: EM (単粒子) / 解像度: 2.87 Å 52828 9ic3 EMDB-52828, PDB-9ic3: Chimeric mitochondrial DNA polymerase gamma ternary complex (hAmB) in mouse-like error-editing conformer (composite) 手法: EM (単粒子) / 解像度: 2.96 Å
化合物	ChemComp-CA: Unknown entry ChemComp-DCP: 2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE
由来	mus musculus (ハツカネズミ) synthetic construct (人工物) homo sapiens (ヒト)
キーワード	TRANSFERASE / Mitochondrial DNA polymerase