2keb

NMR solution structure of the N-terminal domain of the DNA polymerase alpha p68 subunit

spinqualitylabelsall models 2keb, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2keb is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: POLA2 (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum 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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed DNA polymerase alpha-primase (pol-prim) plays a central role in DNA replication in higher eukaryotes, initiating synthesis on both leading and lagging strand single-stranded DNA templates. Pol-prim consists of a primase heterodimer that synthesizes RNA primers, a DNA polymerase that extends them, and a fourth subunit, p68 (also termed B-subunit), that is thought to regulate the complex. Although significant knowledge about single-subunit primases of prokaryotes has accumulated, the functions and regulation of pol-prim remain poorly understood. In the SV40 replication model, the p68 subunit is required for primosome activity and binds directly to the hexameric viral helicase T antigen, suggesting a functional link between T antigen-p68 interaction and primosome activity. To explore this link, we first mapped the interacting regions of the two proteins and discovered a previously unrecognized N-terminal globular domain of p68 (p68N) that physically interacts with the T antigen helicase domain. NMR spectroscopy was used to determine the solution structure of p68N and map its interface with the T antigen helicase domain. Structure-guided mutagenesis of p68 residues in the interface diminished T antigen-p68 interaction, confirming the interaction site. SV40 primosome activity of corresponding pol-prim mutants decreased in proportion to the reduction in p68N-T antigen affinity, confirming that p68-T antigen interaction is vital for primosome function. A model is presented for how this interaction regulates SV40 primosome activity, and the implications of our findings are discussed in regard to the molecular mechanisms of eukaryotic DNA replication initiation. Structure of a DNA polymerase alpha-primase domain that docks on the SV40 helicase and activates the viral primosome.,Huang H, Weiner BE, Zhang H, Fuller BE, Gao Y, Wile BM, Zhao K, Arnett DR, Chazin WJ, Fanning E J Biol Chem. 2010 May 28;285(22):17112-22. Epub 2010 Mar 16. PMID:20234039 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase

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