4e2i

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The Complex Structure of the SV40 Helicase Large T Antigen and p68 Subunit of DNA Polymerase Alpha-PrimaseThe Complex Structure of the SV40 Helicase Large T Antigen and p68 Subunit of DNA Polymerase Alpha-Primase

Structural highlights

4e2i is a 23 chain structure with sequence from Human and Polyomavirus maccacae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:POLA2 (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DPOA2_HUMAN] May play an essential role at the early stage of chromosomal DNA replication by coupling the polymerase alpha/primase complex to the cellular replication machinery (By similarity).

Publication Abstract from PubMed

DNA polymerase alpha-primase (Pol-prim) plays an essential role in eukaryotic DNA replication, initiating synthesis of the leading strand and of each Okazaki fragment on the lagging strand. Pol-prim is composed of a primase heterodimer that synthesizes an RNA primer, a DNA polymerase subunit that extends the primer, and a regulatory B-subunit (p68) without apparent enzymatic activity. Pol-prim is thought to interact with eukaryotic replicative helicases, forming a dynamic multiprotein assembly that displays primosome activity. At least three subunits of Pol-prim interact physically with the hexameric replicative helicase SV40 large T antigen, constituting a simple primosome that is active in vitro. However, structural understanding of these interactions and their role in viral chromatin replication in vivo remains incomplete. Here, we report the detailed large T antigen-p68 interface, as revealed in a co-crystal structure and validated by site-directed mutagenesis, and we demonstrate its functional importance in activating the SV40 primosome in cell-free reactions with purified Pol-prim, as well as in monkey cells in vivo.

Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase alpha-primase.,Zhou B, Arnett DR, Yu X, Brewster A, Sowd GA, Xie CL, Vila S, Gai D, Fanning E, Chen XS J Biol Chem. 2012 Aug 3;287(32):26854-66. doi: 10.1074/jbc.M112.363655. Epub 2012, Jun 14. PMID:22700977[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Zhou B, Arnett DR, Yu X, Brewster A, Sowd GA, Xie CL, Vila S, Gai D, Fanning E, Chen XS. Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase alpha-primase. J Biol Chem. 2012 Aug 3;287(32):26854-66. doi: 10.1074/jbc.M112.363655. Epub 2012, Jun 14. PMID:22700977 doi:10.1074/jbc.M112.363655

4e2i, resolution 5.00Å

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