Crystal structure of the conserved core of the herpes simplex virus transcriptional regulatory protein VP16

Genes Dev. 1999 Jul 1;13(13):1692-703. doi: 10.1101/gad.13.13.1692.

Abstract

On infection, the herpes simplex virus (HSV) virion protein VP16 (Vmw65; alphaTIF) forms a transcriptional regulatory complex-the VP16-induced complex-with two cellular proteins, HCF and Oct-1, on VP16-responsive cis-regulatory elements in HSV immediate-early promoters called TAATGARAT. Comparison of different HSV VP16 sequences reveals a conserved core region that is sufficient for VP16-induced complex formation. The crystal structure of the VP16 core has been determined at 2.1 A resolution. The results reveal a novel, seat-like protein structure. Together with the activity of mutant VP16 proteins, the structure of free VP16 suggests that it contains (1) a disordered carboxy-terminal region that associates with HCF, Oct-1, and DNA in the VP16-induced complex, and (2) a structured region involved in virion assembly and possessing a novel DNA-binding surface that differentiates among TAATGARAT VP16-response elements.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Crystallization
  • Crystallography, X-Ray
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Viral
  • Herpes Simplex Virus Protein Vmw65 / chemistry*
  • Herpes Simplex Virus Protein Vmw65 / genetics
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Herpesviridae / chemistry
  • Host Cell Factor C1
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Octamer Transcription Factor-1
  • Protein Conformation*
  • Recombinant Fusion Proteins / genetics
  • Regulatory Sequences, Nucleic Acid
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Simplexvirus / chemistry*
  • Simplexvirus / physiology
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • Herpes Simplex Virus Protein Vmw65
  • Host Cell Factor C1
  • Macromolecular Substances
  • Octamer Transcription Factor-1
  • Recombinant Fusion Proteins
  • Transcription Factors
  • DNA