5VBN

Crystal Structure of human DNA polymerase epsilon B-subunit in complex with C-terminal domain of catalytic subunit

Summary for 5VBN

• Entry DOI: 10.2210/pdb5vbn/pdb
• Descriptor: DNA polymerase epsilon subunit 2, DNA polymerase epsilon catalytic subunit A, SULFATE ION, ... (5 entities in total)
• Functional Keywords: replication, dna replication, polymerase, dna polymerase, dna polymerase epsilon, b-subunit, catalytic subunit, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 152689.81

Authors

Baranovskiy, A.G.,Gu, J.,Suwa, Y.,Babayeva, N.D.,Tahirov, T.H. (deposition date: 2017-03-29, release date: 2017-08-02, Last modification date: 2024-03-06)

Primary citation

Baranovskiy, A.G.,Gu, J.,Babayeva, N.D.,Kurinov, I.,Pavlov, Y.I.,Tahirov, T.H.
Crystal structure of the human Pol B-subunit in complex with the C-terminal domain of the catalytic subunit.
J. Biol. Chem., 292:15717-15730, 2017

PubMed Abstract: The eukaryotic B-family DNA polymerases include four members: Polα, Polδ, Polϵ, and Polζ, which share common architectural features, such as the exonuclease/polymerase and C-terminal domains (CTDs) of catalytic subunits bound to indispensable B-subunits, which serve as scaffolds that mediate interactions with other components of the replication machinery. Crystal structures for the B-subunits of Polα and Polδ/Polζ have been reported: the former within the primosome and separately with CTD and the latter with the N-terminal domain of the C-subunit. Here we present the crystal structure of the human Polϵ B-subunit (p59) in complex with CTD of the catalytic subunit (p261). The structure revealed a well defined electron density for p261 and the phosphodiesterase and oligonucleotide/oligosaccharide-binding domains of p59. However, electron density was missing for the p59 N-terminal domain and for the linker connecting it to the phosphodiesterase domain. Similar to Polα, p261 of Polϵ contains a three-helix bundle in the middle and zinc-binding modules on each side. Intersubunit interactions involving 11 hydrogen bonds and numerous hydrophobic contacts account for stable complex formation with a buried surface area of 3094 Å Comparative structural analysis of p59-p261 with the corresponding Polα complex revealed significant differences between the B-subunits and CTDs, as well as their interaction interfaces. The B-subunit of Polδ/Polζ also substantially differs from B-subunits of either Polα or Polϵ. This work provides a structural basis to explain biochemical and genetic data on the importance of B-subunit integrity in replisome function .

PubMed: 28747437
DOI: 10.1074/jbc.M117.792705

Experimental method

X-RAY DIFFRACTION (2.35 Å)