- EMDB-42982: Human mitochondrial DNA polymerase catalytic subunit, PolG, in an... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-42982
タイトル
Human mitochondrial DNA polymerase catalytic subunit, PolG, in an APO conformation
マップデータ
試料
複合体: mitochondrial DNA polymerase catalytic subunit, PolG
タンパク質・ペプチド: DNA polymerase subunit gamma-1
キーワード
DNA BINDING PROTEIN / DNA polymerase / mitochondrial DNA replication / DNA polymerase catalytic subunit / DNA BINDING PROTEIN-DNA complex
機能・相同性
機能・相同性情報
gamma DNA polymerase complex / mitochondrial DNA replication / single-stranded DNA 3'-5' DNA exonuclease activity / 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 / DNA metabolic process / DNA replication proofreading / mitochondrial nucleoid / 付加脱離酵素(リアーゼ); 炭素-酸素リアーゼ類; その他の炭素-酸素リアーゼ / 5'-deoxyribose-5-phosphate lyase activity / 3'-5' exonuclease activity ...gamma DNA polymerase complex / mitochondrial DNA replication / single-stranded DNA 3'-5' DNA exonuclease activity / 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 / DNA metabolic process / DNA replication proofreading / mitochondrial nucleoid / 付加脱離酵素(リアーゼ); 炭素-酸素リアーゼ類; その他の炭素-酸素リアーゼ / 5'-deoxyribose-5-phosphate lyase activity / 3'-5' exonuclease activity / base-excision repair, gap-filling / base-excision repair / DNA-templated DNA replication / protease binding / DNA-directed DNA polymerase / DNA-directed DNA polymerase activity / mitochondrial matrix / intracellular membrane-bounded organelle / chromatin binding / protein-containing complex / mitochondrion / DNA binding 類似検索 - 分子機能
DNA-directed DNA-polymerase, family A, mitochondria / DNA mitochondrial polymerase, exonuclease domain / : / DNA mitochondrial polymerase exonuclease domain / DNA-directed DNA polymerase, family A, conserved site / DNA polymerase family A signature. / DNA-directed DNA polymerase, family A, palm domain / DNA polymerase A domain / Ribonuclease H-like superfamily / DNA/RNA polymerase superfamily 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS)
Z01 ES065078
米国
National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS)
Z01 ES065080
米国
National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS)
ZIC ES 103326
米国
引用
ジャーナル: Nucleic Acids Res / 年: 2024 タイトル: Coordinated DNA polymerization by Polγ and the region of LonP1 regulated proteolysis. 著者: Amanda A Riccio / Asia J Brannon / Juno M Krahn / Jonathan Bouvette / Jason G Williams / Mario J Borgnia / William C Copeland / 要旨: The replicative mitochondrial DNA polymerase, Polγ, and its protein regulation are essential for the integrity of the mitochondrial genome. The intricacies of Polγ regulation and its interactions ...The replicative mitochondrial DNA polymerase, Polγ, and its protein regulation are essential for the integrity of the mitochondrial genome. The intricacies of Polγ regulation and its interactions with regulatory proteins, which are essential for fine-tuning polymerase function, remain poorly understood. Misregulation of the Polγ heterotrimer, consisting of (i) PolG, the polymerase catalytic subunit and (ii) PolG2, the accessory subunit, ultimately results in mitochondrial diseases. Here, we used single particle cryo-electron microscopy to resolve the structure of PolG in its apoprotein state and we captured Polγ at three intermediates within the catalytic cycle: DNA bound, engaged, and an active polymerization state. Chemical crosslinking mass spectrometry, and site-directed mutagenesis uncovered the region of LonP1 engagement of PolG, which promoted proteolysis and regulation of PolG protein levels. PolG2 clinical variants, which disrupted a stable Polγ complex, led to enhanced LonP1-mediated PolG degradation. Overall, this insight into Polγ aids in an understanding of mitochondrial DNA replication and characterizes how machinery of the replication fork may be targeted for proteolytic degradation when improperly functioning.