The Crystal Structure of the Herpes Simplex Virus 1 ssDNA-binding Protein Suggests the Structural Basis for Flexible, Cooperative Single-stranded DNA Binding

Paul A. Tucker,Marina Mapelli,Santosh Panjikar

doi:10.1074/jbc.m406780200

Paul A. Tucker, Marina Mapelli + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m406780200

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Abstract

All organisms including animal viruses use specific proteins to bind single-stranded DNA rapidly in a non-sequence-specific, flexible, and cooperative manner during the DNA replication process. The crystal structure of a 60-residue C-terminal deletion construct of ICP8, the major single-stranded DNA-binding protein from herpes simplex virus-1, was determined at 3.0 A resolution. The structure reveals a novel fold, consisting of a large N-terminal domain (residues 9-1038) and a small C-terminal domain (residues 1049-1129). On the basis of the structure and the nearest neighbor interactions in the crystal, we have presented a model describing the site of single-stranded DNA binding and explaining the basis for cooperative binding. This model agrees with the beaded morphology observed in electron micrographs.

Highlights

Viruses of the Herpesviridae family infect almost all vertebrates, including man, causing a variety of diseases
Of the seven viruses identified as human infectious agents, herpes simplex virus-1 (HSV-1)1 is the prototype of the ␣herpesvirus subfamily and of the family as a whole
There is evidence that it binds to the C terminus of the OBP and stimulates its helicase activity [5, 6], that it promotes the helicase activity of the viral helicase-primase complex (UL5-UL8-UL52) [7], and that it modulates the processivity of the viral polymerase (UL30) [8]

Summary

Introduction

Viruses of the Herpesviridae family infect almost all vertebrates, including man, causing a variety of diseases. The crystal structure of a 60-residue C-terminal deletion construct of ICP8, the major single-stranded DNA-binding protein from herpes simplex virus-1, was determined at 3.0 Å resolution.

Results

Conclusion