Abstract
The 1.74-Å crystal structure of the human transcription cofactor PC4 in complex with a single-stranded 20-mer oligonucleotide reveals how symmetry-related β-surfaces of the protein homodimer interact with juxtaposed 5-nucleotide DNA regions running in opposite directions. The structure explains high-affinity binding of PC4 to the complementary strands of unwinding duplex DNA, and it suggests the cofactor may have a role in relaxing negative supercoils or exposing unpaired bases for sequence-specific recognition by other biomolecules.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Accession codes
References
Kaiser, K., Stelzer, G. & Meisterernst, M. EMBO J. 14, 3520–3527 (1995).
Fukuda, A. et al. Mol. Cell. Biol. 24, 6525–6535 (2004).
Werten, S. et al. J. Mol. Biol. 276, 367–377 (1998).
Brandsen, J. et al. Nat. Struct. Biol. 4, 900–903 (1997).
Werten, S., Wechselberger, R., Boelens, R., Van der Vliet, P.C. & Kaptein, R. J. Biol. Chem. 274, 3693–3699 (1999).
Werten, S. et al. EMBO J. 17, 5103–5111 (1998).
Ballard, D.W., Philbrick, W.M. & Bothwell, A.L. J. Biol. Chem. 263, 8450–8457 (1988).
Wang, J.-Y., Sarker, A.H., Cooper, P.K. & Volkert, M.R. Mol. Cell. Biol. 24, 6084–6093 (2004).
Calvo, O. & Manley, J.L. EMBO J. 24, 1009–1020 (2005).
Dekker, J. et al. EMBO J. 16, 1455–1463 (1997).
Acknowledgements
We thank A. Mitschler and the beamline staff at the European Synchrotron Radiation Facility for assistance during data collection. S.W. was supported by a Human Frontiers Science Project long-term fellowship.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Fig. 1
Example of ssDNA electron density (PDF 1599 kb)
Supplementary Fig. 2
Overall structure of the PC4–ssDNA complex (PDF 2554 kb)
Supplementary Fig. 3
Annotated sequence alignment of the conserved region of PC4 (PDF 3620 kb)
Supplementary Fig. 4
Formation of infinite helical protein-ssDNA filaments within the crystal (PDF 2160 kb)
Supplementary Table 1
Data collection and refinement statistics (PDF 1258 kb)
Rights and permissions
About this article
Cite this article
Werten, S., Moras, D. A global transcription cofactor bound to juxtaposed strands of unwound DNA. Nat Struct Mol Biol 13, 181–182 (2006). https://doi.org/10.1038/nsmb1044
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nsmb1044
This article is cited by
-
Sub1/PC4, a multifaceted factor: from transcription to genome stability
Current Genetics (2017)
-
PC4 promotes genome stability and DNA repair through binding of ssDNA at DNA damage sites
Oncogene (2016)
-
Chemical shift assignments of the homodimer protein SP_0782 (7–79) from Streptococcus pneumoniae
Biomolecular NMR Assignments (2016)
-
The Sub1 nuclear protein protects DNA from oxidative damage
Molecular and Cellular Biochemistry (2016)
-
Substitution of tryptophan 89 with tyrosine switches the DNA binding mode of PC4
Scientific Reports (2015)
