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Originally published In Press as doi:10.1074/jbc.M406780200 on October 26, 2004

J. Biol. Chem., Vol. 280, Issue 4, 2990-2997, January 28, 2005
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The Crystal Structure of the Herpes Simplex Virus 1 ssDNA-binding Protein Suggests the Structural Basis for Flexible, Cooperative Single-stranded DNA Binding*{boxs}

Marina Mapelli{ddagger}§, Santosh Panjikar{ddagger}, and Paul A. Tucker¶

From the European Molecular Biology Laboratory, Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany

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 Å 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.


Received for publication, June 17, 2004 , and in revised form, October 25, 2004.

The atomic coordinates and structure factors (code 1URJ) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains supplemental figures.

{ddagger} Both authors contributed equally to this work.

§ Present address: European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy.

To whom correspondence should be addressed. Tel.: 49-40-8990-2129; Fax: 49-40-8990-2149; E-mail: tucker{at}embl-hamburg.de.


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