3IKM

Crystal structure of human mitochondrial DNA polymerase holoenzyme

Summary for 3IKM

• Entry DOI: 10.2210/pdb3ikm/pdb
• Descriptor: DNA polymerase subunit gamma-1, DNA polymerase subunit gamma-2 (2 entities in total)
• Functional Keywords: human mitochondrial dna polymerase, disease mutation, dna replication, dna-binding, dna-directed dna polymerase, magnesium, mitochondrion, neuropathy, nucleotidyltransferase, progressive external ophthalmoplegia, transferase, transit peptide
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion : P54098 Q9UHN1
• Total number of polymer chains: 6
• Total formula weight: 459800.98

Authors

Lee, Y.-S.,Kennedy, W.D.,Yin, Y.W. (deposition date: 2009-08-06, release date: 2009-11-03, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.24 Å)