Crystal structure of the human primase

Andrey G. Baranovskiy, Yinbo Zhang, Yoshiaki Suwa, Nigar D. Babayeva, Jianyou Gu, Youri I Pavlov, Tahir H Tahirov

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

DNA replication in bacteria and eukaryotes requires the activity of DNA primase, a DNA-dependent RNA polymerase that lays short RNA primers for DNA polymerases. Eukaryotic and archaeal primases are heterodimers consisting of small catalytic and large accessory subunits, both of which are necessary for RNA primer synthesis. Understanding of RNA synthesis priming in eukaryotes is currently limited due to the lack of crystal structures of the full-length primase and its complexes with substrates in initiation and elongation states. Here we report the crystal structure of the full-length human primase, revealing the precise overall organization of the enzyme, the relative positions of its functional domains, and the mode of its interaction with modeled DNA and RNA. The structure indicates that the dramatic conformational changes in primase are necessary to accomplish the initiation and then elongation of RNAsynthesis. The presence of a long linker between the N- and C-terminal domains of p58 provides the structural basis for the bulk of enzyme's conformational flexibility. Deletion of most of this linker affected the initiation and elongation steps of the primer synthesis.

Original languageEnglish (US)
Pages (from-to)5635-5646
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number9
DOIs
StatePublished - Feb 27 2015

Fingerprint

DNA Primase
Crystal structure
Elongation
Eukaryota
RNA
DNA
Accessories
DNA-Directed DNA Polymerase
Enzymes
DNA-Directed RNA Polymerases
DNA Replication
Bacteria
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Baranovskiy, A. G., Zhang, Y., Suwa, Y., Babayeva, N. D., Gu, J., Pavlov, Y. I., & Tahirov, T. H. (2015). Crystal structure of the human primase. Journal of Biological Chemistry, 290(9), 5635-5646. https://doi.org/10.1074/jbc.M114.624742

Crystal structure of the human primase. / Baranovskiy, Andrey G.; Zhang, Yinbo; Suwa, Yoshiaki; Babayeva, Nigar D.; Gu, Jianyou; Pavlov, Youri I; Tahirov, Tahir H.

In: Journal of Biological Chemistry, Vol. 290, No. 9, 27.02.2015, p. 5635-5646.

Research output: Contribution to journalArticle

Baranovskiy, AG, Zhang, Y, Suwa, Y, Babayeva, ND, Gu, J, Pavlov, YI & Tahirov, TH 2015, 'Crystal structure of the human primase', Journal of Biological Chemistry, vol. 290, no. 9, pp. 5635-5646. https://doi.org/10.1074/jbc.M114.624742
Baranovskiy AG, Zhang Y, Suwa Y, Babayeva ND, Gu J, Pavlov YI et al. Crystal structure of the human primase. Journal of Biological Chemistry. 2015 Feb 27;290(9):5635-5646. https://doi.org/10.1074/jbc.M114.624742
Baranovskiy, Andrey G. ; Zhang, Yinbo ; Suwa, Yoshiaki ; Babayeva, Nigar D. ; Gu, Jianyou ; Pavlov, Youri I ; Tahirov, Tahir H. / Crystal structure of the human primase. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 9. pp. 5635-5646.
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