8D33

Human mitochondrial DNA polymerase gamma ternary complex with GC basepair

8D33 の概要

• エントリーDOI: 10.2210/pdb8d33/pdb
• EMDBエントリー: 27154 27155
• 分子名称: DNA polymerase subunit gamma-1, DNA polymerase subunit gamma-2, mitochondrial, DNA (5'-D(P*AP*AP*AP*AP*CP*GP*AP*CP*GP*GP*CP*CP*AP*GP*TP*GP*CP*CP*AP*TP*AP*C)-3'), ... (6 entities in total)
• 機能のキーワード: dna-binding protein, dna polymerase, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 268708.82

構造登録者

Park, J.,Yin, Y.W. (登録日: 2022-05-31, 公開日: 2023-05-24, 最終更新日: 2025-06-04)

主引用文献

Park, J.,Herrmann, G.K.,Mitchell, P.G.,Sherman, M.B.,Yin, Y.W.
Pol gamma coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.
Nat.Struct.Mol.Biol., 30:812-823, 2023

PubMed Abstract: Accurate replication of mitochondrial DNA (mtDNA) by DNA polymerase γ (Polγ) is essential for maintaining cellular energy supplies, metabolism, and cell cycle control. To illustrate the structural mechanism for Polγ coordinating polymerase (pol) and exonuclease (exo) activities to ensure rapid and accurate DNA synthesis, we determined four cryo-EM structures of Polγ captured after accurate or erroneous incorporation to a resolution of 2.4-3.0 Å. The structures show that Polγ employs a dual-checkpoint mechanism to sense nucleotide misincorporation and initiate proofreading. The transition from replication to error editing is accompanied by increased dynamics in both DNA and enzyme, in which the polymerase relaxes its processivity and the primer-template DNA unwinds, rotates, and backtracks to shuttle the mismatch-containing primer terminus 32 Å to the exo site for editing. Our structural and functional studies also provide a foundation for analyses of Polγ mutation-induced human diseases and aging.

PubMed: 37202477
DOI: 10.1038/s41594-023-00980-2

実験手法

ELECTRON MICROSCOPY (2.46 Å)