The herpes viral transcription factor ICP4 forms a novel DNA recognition complex

Nucleic Acids Research
Richard B TunnicliffeAlexander P Golovanov

Abstract

The transcription factor ICP4 from herpes simplex virus has a central role in regulating the gene expression cascade which controls viral infection. Here we present the crystal structure of the functionally essential ICP4 DNA binding domain in complex with a segment from its own promoter, revealing a novel homo-dimeric fold. We also studied the complex in solution by small angle X-Ray scattering, nuclear magnetic resonance and surface-plasmon resonance which indicated that, in addition to the globular domain, a flanking intrinsically disordered region also recognizes DNA. Together the data provides a rationale for the bi-partite nature of the ICP4 DNA recognition consensus sequence as the globular and disordered regions bind synergistically to adjacent DNA motifs. Therefore in common with its eukaryotic host, the viral transcription factor ICP4 utilizes disordered regions to enhance the affinity and tune the specificity of DNA interactions in tandem with a globular domain.

References

Apr 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·R W Honess, B Roizman
Aug 14, 1989·Biochimica Et Biophysica Acta·S S Leinbach, L S Heath
Aug 1, 1985·Journal of Virology·D W Metzler, K W Wilcox
Jan 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·P J Godowski, D M Knipe
Jan 5, 1993·Journal of Molecular Biology·G D Van DuyneJ Clardy
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·B GuN A DeLuca
Feb 1, 1996·Journal of Virology·K XiaD M Knipe
Sep 15, 1998·Journal of Molecular Biology·M A El Hassan, C R Calladine
Jul 10, 2002·Biochemistry·Dong WangJindrich Kopecek
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 22, 2004·Journal of the American Chemical Society·Alexander P GolovanovLu-Yun Lian
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Aug 22, 2006·Trends in Biochemical Sciences·Colyn Crane-RobinsonPeter L Privalov
Jun 22, 2007·Journal of Virology·Ruhul H Kuddus, Neal A DeLuca
May 26, 2009·Acta Crystallographica. Section D, Biological Crystallography·Thomas C TerwilligerLi Wei Hung
Oct 15, 2009·International Journal of Pharmaceutics·Johannes GeigerCarsten Rudolph
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Sep 16, 2011·Molecular BioSystems·Dana Vuzman, Yaakov Levy
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Nov 3, 2011·Current Protein & Peptide Science·Veronique Receveur-Brechot, Dominique Durand
Jan 13, 2012·Current Opinion in Biotechnology·Christopher V Rao

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Citations

Jun 17, 2020·Investigative Ophthalmology & Visual Science·Oleg AlekseevJane Azizkhan-Clifford
May 1, 2021·International Journal of Molecular Sciences·Michael SeyffertCornel Fraefel
Jul 25, 2021·Current Opinion in Structural Biology·Sagie BrodskyNaama Barkai
Jun 16, 2021·Annual Review of Virology·Andrew E Hale, Nathaniel J Moorman

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Methods Mentioned

BETA
NMR
X-Ray
nuclear
light
surface-plasmon resonance
surface plasmon resonance
gel filtration
size
light scattering
chip

Software Mentioned

Fast EP
Clustal omega
Chimeras
AutoBuild
Sedfit
DAMAVER
Phenix
ProteOn Manager
MONSA
SigmaPlot

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