Substitution of tryptophan 89 with tyrosine switches the DNA binding mode of PC4

Scientific Reports
Jinguang HuangYouliang Peng

Abstract

PC4, a well-known general transcription cofactor, has multiple functions in transcription and DNA repair. Residue W89, is engaged in stacking interactions with DNA in PC4, but substituted by tyrosine in some PC4 orthologous proteins. In order to understand the consequences and reveal the molecular details of this substitution we have determined the crystal structures of the PC4 orthologue MoSub1 and a PC4 W89Y mutant in complex with DNA. In the structure of MoSub1-DNA complex, Y74 interacts directly with a single nucleotide of oligo DNA. By comparison, the equivalent residue, W89 in wild type PC4 interacts with two nucleotides and the base of the second nucleotide has distinct orientation relative to that of the first one. A hydrophobic patch around W89 that favours interaction with two nucleotides is not formed in the PC4 W89Y mutant. Therefore, the change of the surface hydrophobicity around residue 89 results in a difference between the modes of DNA interaction. These results indicate that the conserved Y74 in MoSub1 or W89 in PC4, are not only key residues in making specific interactions with DNA but also required to determine the DNA binding mode of PC4 proteins.

References

Feb 20, 1991·Journal of Molecular Biology·D Bordo, P Argos
Sep 6, 1996·The Journal of Biological Chemistry·N L HenryR D Kornberg
Nov 14, 1997·Nature Structural Biology·J BrandsenP Gros
Sep 2, 1998·The EMBO Journal·S WertenM Meisterernst
Jun 29, 2005·Acta Crystallographica. Section D, Biological Crystallography·Pavel V AfoninePaul D Adams
Jan 18, 2006·Nature Structural & Molecular Biology·Sebastiaan Werten, Dino Moras
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Feb 11, 2009·Molecular and Cellular Biology·Emanuel RosoninaJames L Manley
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Arounie TavenetJoël Acker
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 23, 2010·RNA Biology·Christine Conesa, Joël Acker
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Sep 17, 2011·Journal of Chemical Information and Modeling·Roman A Laskowski, Mark B Swindells
Nov 8, 2011·Molecular Cell·Timothy W SikorskiStephen Buratowski
May 19, 2012·The Journal of Biological Chemistry·Huidong ZhangCharles C Richardson
Sep 6, 2012·Acta Crystallographica. Section D, Biological Crystallography·Jinguang HuangYouliang Peng

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Citations

May 7, 2020·Burns and Trauma·Fengying LiaoChunmeng Shi
May 2, 2020·Nucleic Acids Research·Stanley T CrookeXue-Hai Liang
Feb 2, 2021·Biochemical and Biophysical Research Communications·Qing WangChunmeng Shi
Mar 24, 2020·Journal of the American Chemical Society·Malwina Hyjek-SkładanowskaMarcin Nowotny
Feb 19, 2021·The Journal of Biological Chemistry·Stanley T CrookeRosanne M Crooke

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Methods Mentioned

BETA
PCR
gel-filtration
isothermal titration calorimetry
X-ray
electrophoretic mobility shift

Software Mentioned

LigPlot
MolProbity
PyMOL
PyMOL Molecular Graphics system
Boxshade
Phaser
PHENIX
Origin
ClustalW
CCP4

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