3IKM

Crystal structure of human mitochondrial DNA polymerase holoenzyme

3IKM の概要

• エントリーDOI: 10.2210/pdb3ikm/pdb
• 分子名称: DNA polymerase subunit gamma-1, DNA polymerase subunit gamma-2 (2 entities in total)
• 機能のキーワード: human mitochondrial dna polymerase, disease mutation, dna replication, dna-binding, dna-directed dna polymerase, magnesium, mitochondrion, neuropathy, nucleotidyltransferase, progressive external ophthalmoplegia, transferase, transit peptide
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Mitochondrion : P54098 Q9UHN1
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 459800.98

構造登録者

Lee, Y.-S.,Kennedy, W.D.,Yin, Y.W. (登録日: 2009-08-06, 公開日: 2009-11-03, 最終更新日: 2024-02-21)

主引用文献

Lee, Y.S.,Kennedy, W.D.,Yin, Y.W.
Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations.
Cell(Cambridge,Mass.), 139:312-324, 2009

PubMed Abstract: Human mitochondrial DNA polymerase (Pol gamma) is the sole replicase in mitochondria. Pol gamma is vulnerable to nonselective antiretroviral drugs and is increasingly associated with mutations found in patients with mitochondriopathies. We determined crystal structures of the human heterotrimeric Pol gamma holoenzyme and, separately, a variant of its processivity factor, Pol gammaB. The holoenzyme structure reveals an unexpected assembly of the mitochondrial DNA replicase where the catalytic subunit Pol gammaA interacts with its processivity factor primarily via a domain that is absent in all other DNA polymerases. This domain provides a structural module for supporting both the intrinsic processivity of the catalytic subunit alone and the enhanced processivity of holoenzyme. The Pol gamma structure also provides a context for interpreting the phenotypes of disease-related mutations in the polymerase and establishes a foundation for understanding the molecular basis of toxicity of anti-retroviral drugs targeting HIV reverse transcriptase.

PubMed: 19837034
DOI: 10.1016/j.cell.2009.07.050

実験手法

X-RAY DIFFRACTION (3.24 Å)