8UDL

Human Mitochondrial DNA Polymerase Gamma Binary Complex

Summary for 8UDL

• Entry DOI: 10.2210/pdb8udl/pdb
• EMDB information: 42150
• Descriptor: 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'), ... (4 entities in total)
• Functional Keywords: mitochondrial, dna polymerase, transferase, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 263859.85

Authors

Park, J.,Yin, Y.W. (deposition date: 2023-09-28, release date: 2024-06-05, Last modification date: 2025-05-28)

Primary citation

Park, J.,Herrmann, G.K.,Roy, A.,Shumate, C.K.,Cisneros, G.A.,Yin, Y.W.
An interaction network in the polymerase active site is a prerequisite for Watson-Crick base pairing in Pol gamma.
Sci Adv, 10:eadl3214-eadl3214, 2024

PubMed Abstract: The replication accuracy of DNA polymerase gamma (Pol γ) is essential for mitochondrial genome integrity. Mutation of human Pol γ arginine-853 has been linked to neurological diseases. Although not a catalytic residue, Pol γ arginine-853 mutants are void of polymerase activity. To identify the structural basis for the disease, we determined a crystal structure of the Pol γ mutant ternary complex with correct incoming nucleotide 2'-deoxycytidine 5'-triphosphate (dCTP). Opposite to the wild type that undergoes open-to-closed conformational changes when bound to a correct nucleotide that is essential for forming a catalytically competent active site, the mutant complex failed to undergo the conformational change, and the dCTP did not base pair with its Watson-Crick complementary templating residue. Our studies revealed that arginine-853 coordinates an interaction network that aligns the 3'-end of primer and dCTP with the catalytic residues. Disruption of the network precludes the formation of Watson-Crick base pairing and closing of the active site, resulting in an inactive polymerase.

PubMed: 38787958
DOI: 10.1126/sciadv.adl3214

Experimental method

ELECTRON MICROSCOPY (2.37 Å)