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

DOI: 10.1093/nar/gkx419 DOI Help

Authors: Richard B. Tunnicliffe (The University of Manchester) , Michael P. Lockhart-cairns (University of Manchester, Diamond Light Source) , Colin Levy (The University of Manchester) , A. Paul Mould (The University of Manchester) , Thomas A. Jowitt (The University of Manchester) , Hilary Sito (The University of Manchester) , Clair Baldock (University of Manchester) , Rozanne M. Sandri-goldin (University of California) , Alexander P. Golovanov (The University of Manchester, Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research

State: Published (Approved)
Published: May 2017
Diamond Proposal Number(s): 12788 , 8997 , 11534

Open Access Open Access

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.

Journal Keywords: simplexvirus; dna; transcription factor; affinity; crystal structure

Subject Areas: Biology and Bio-materials, Medicine


Instruments: B21-High Throughput SAXS , I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Other Facilities: ESRF

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