9Y4E

Strand displacement state III of Human mitochondrial DNA polymerase gamma ternary complex

9Y4E の概要

• エントリーDOI: 10.2210/pdb9y4e/pdb
• EMDBエントリー: 72480
• 分子名称: DNA polymerase subunit gamma-1, DNA polymerase subunit gamma-2, mitochondrial, DNA (54-MER), ... (5 entities in total)
• 機能のキーワード: dna polymerase gamma, strand displacement, mitochondria, 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: 4
• 化学式量合計: 273949.07

構造登録者

Park, J.,Yin, Y.W. (登録日: 2025-09-03, 公開日: 2026-02-18)

主引用文献

Baruch-Torres, N.,Park, J.,Mora-Garduno, J.,Roy, A.,Singh, A.,Cisneros, G.A.,Brieba, L.G.,Patel, S.S.,Yin, Y.W.
Pol gamma possesses separate metal binding sites for polymerase and strand displacement functions.
Biorxiv, 2026

PubMed Abstract: Accurate replication of mitochondrial genome (mtDNA) integrity, which is essential for cellular metabolism and energy supply, relies primarily on DNA polymerase gamma (Pol γ), Twinkle helicase, and mitochondrial single-stranded DNA binding protein (mtSSB). Twinkle alone exhibits little helicase activity while reports indicate that Pol γ displays from modest to limited unwinding activity. This led us to dissect Pol γ strand displacement activity using structural, biochemical and in silico approaches. Here, we show that human Pol γ carries out robust strand displacement synthesis at physiological concentrations of divalent metal ions which reveals that distinct metal-binding sites can independently regulate DNA synthesis and unwinding activities. We further showed that Pol γ can displace RNA/DNA hybrid with comparable efficiency as DNA/DNA duplex, representing a key implication on RNA primer removal to preserve mtDNA integrity. Our cryo-electron microscopy structures of Pol γ complexed with a template containing downstream dsDNA and an incoming nucleotide revealed the structural mechanism for the strand displacement activity. We identified four conformational states that represent successive stages of DNA unwinding, accompanied by coordinated rearrangement of the downstream DNA and Pol γ elements that mediate strand displacement. This work establishes biochemical and structural mechanisms of Pol γ strand displacement activity, providing fundamental insight into human mitochondrial DNA replication and integrity.

PubMed: 41648309
DOI: 10.64898/2026.01.25.701366

実験手法

ELECTRON MICROSCOPY (3.05 Å)