9IC0

Chimeric mitochondrial DNA polymerase gamma ternary complex (mAhB) in mouse-like error-editing conformer (composite)

9IC0 の概要

• エントリーDOI: 10.2210/pdb9ic0/pdb
• 関連するPDBエントリー: 9G74 9G75 9G77 9IBX 9IBZ 9IC1 9IC3
• EMDBエントリー: 52823
• 分子名称: DNA polymerase subunit gamma-1, DNA polymerase subunit gamma-2, DNA (primer strand), ... (6 entities in total)
• 機能のキーワード: mitochondrial dna polymerase, transferase
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 262027.66

構造登録者

Valenzuela, S.,Falkenberg, M. (登録日: 2025-02-14, 公開日: 2025-06-04)

主引用文献

Corra, S.,Zuppardo, A.,Valenzuela, S.,Jenninger, L.,Cerutti, R.,Sillamaa, S.,Hoberg, E.,Johansson, K.A.S.,Rovsnik, U.,Volta, S.,Silva-Pinheiro, P.,Davis, H.,Trifunovic, A.,Minczuk, M.,Gustafsson, C.M.,Suomalainen, A.,Zeviani, M.,Macao, B.,Zhu, X.,Falkenberg, M.,Viscomi, C.
Modelling POLG mutations in mice unravels a critical role of POL gamma Beta in regulating phenotypic severity.
Nat Commun, 16:4782-4782, 2025

PubMed Abstract: 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.

PubMed: 40404629
DOI: 10.1038/s41467-025-60059-y

実験手法

ELECTRON MICROSCOPY (3.24 Å)