4Y97

Crystal Structure of human Pol alpha B-subunit in complex with C-terminal domain of catalytic subunit

Summary for 4Y97

• Entry DOI: 10.2210/pdb4y97/pdb
• Descriptor: DNA polymerase alpha subunit B, DNA polymerase alpha catalytic subunit, ZINC ION, ... (4 entities in total)
• Functional Keywords: human dna polymerase alpha, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 349350.62

Authors

Suwa, Y.,Gu, J.,Baranovskiy, A.G.,Babayeva, N.D.,Tahirov, T.H. (deposition date: 2015-02-17, release date: 2015-04-15, Last modification date: 2023-09-27)

Primary citation

Suwa, Y.,Gu, J.,Baranovskiy, A.G.,Babayeva, N.D.,Pavlov, Y.I.,Tahirov, T.H.
Crystal Structure of the Human Pol alpha B Subunit in Complex with the C-terminal Domain of the Catalytic Subunit.
J.Biol.Chem., 290:14328-14337, 2015

PubMed Abstract: In eukaryotic DNA replication, short RNA-DNA hybrid primers synthesized by primase-DNA polymerase α (Prim-Pol α) are needed to start DNA replication by the replicative DNA polymerases, Pol δ and Pol ϵ. The C terminus of the Pol α catalytic subunit (p180C) in complex with the B subunit (p70) regulates the RNA priming and DNA polymerizing activities of Prim-Pol α. It tethers Pol α and primase, facilitating RNA primer handover from primase to Pol α. To understand these regulatory mechanisms and to reveal the details of human Pol α organization, we determined the crystal structure of p70 in complex with p180C. The structured portion of p70 includes a phosphodiesterase (PDE) domain and an oligonucleotide/oligosaccharide binding (OB) domain. The N-terminal domain and the linker connecting it to the PDE domain are disordered in the reported crystal structure. The p180C adopts an elongated asymmetric saddle shape, with a three-helix bundle in the middle and zinc-binding modules (Zn1 and Zn2) on each side. The extensive p180C-p70 interactions involve 20 hydrogen bonds and a number of hydrophobic interactions resulting in an extended buried surface of 4080 Å(2). Importantly, in the structure of the p180C-p70 complex with full-length p70, the residues from the N-terminal to the OB domain contribute to interactions with p180C. The comparative structural analysis revealed both the conserved features and the differences between the human and yeast Pol α complexes.

PubMed: 25847248
DOI: 10.1074/jbc.M115.649954

Experimental method

X-RAY DIFFRACTION (2.51 Å)