5F0Q

Crystal structure of C-terminal domain of the human DNA primase large subunit with bound DNA template/RNA primer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome.

Baranovskiy, A.G.Babayeva, N.D.Zhang, Y.Gu, J.Suwa, Y.Pavlov, Y.I.Tahirov, T.H.

(2016) J Biol Chem 291: 10006-10020

  • DOI: https://doi.org/10.1074/jbc.M116.717405
  • Primary Citation of Related Structures:  
    5EXR, 5F0Q, 5F0S

  • PubMed Abstract: 

    The human primosome, a 340-kilodalton complex of primase and DNA polymerase α (Polα), synthesizes chimeric RNA-DNA primers to be extended by replicative DNA polymerases δ and ϵ. The intricate mechanism of concerted primer synthesis by two catalytic centers was an enigma for over three decades. Here we report the crystal structures of two key complexes, the human primosome and the C-terminal domain of the primase large subunit (p58C) with bound DNA/RNA duplex. These structures, along with analysis of primase/polymerase activities, provide a plausible mechanism for all transactions of the primosome including initiation, elongation, accurate counting of RNA primer length, primer transfer to Polα, and concerted autoregulation of alternate activation/inhibition of the catalytic centers. Our findings reveal a central role of p58C in the coordinated actions of two catalytic domains in the primosome and ultimately could impact the design of anticancer drugs.


  • Organizational Affiliation

    From the Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center and.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA primase large subunit
A, B
191Homo sapiensMutation(s): 0 
Gene Names: PRIM2PRIM2A
EC: 2.7.7
UniProt & NIH Common Fund Data Resources
Find proteins for P49643 (Homo sapiens)
Explore P49643 
Go to UniProtKB:  P49643
PHAROS:  P49643
GTEx:  ENSG00000146143 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49643
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
RNA (5'-R(P*GP*GP*CP*GP*GP*C)-3')
C, E
6Homo sapiens
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*GP*CP*CP*GP*CP*CP*AP*AP*CP*AP*TP*A)-3')
D, F
12Homo sapiens
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.223 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 122.507α = 90
b = 126.002β = 90
c = 83.942γ = 90
Software Package:
Software NamePurpose
HKL-3000data collection
HKL-3000data scaling
CNSrefinement
PDB_EXTRACTdata extraction
HKL-3000data reduction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM101167
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesCA036727
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM103403

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-23
    Type: Initial release
  • Version 1.1: 2016-03-30
    Changes: Database references
  • Version 1.2: 2016-06-01
    Changes: Database references
  • Version 1.3: 2017-09-20
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.4: 2017-11-01
    Changes: Author supporting evidence
  • Version 1.5: 2019-12-04
    Changes: Author supporting evidence
  • Version 1.6: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description