The DNA-binding domain of human papillomavirus type 18 E1. Crystal structure, dimerization, and DNA binding

Auster, A. S., Joshua-Tor, L. (January 2004) The DNA-binding domain of human papillomavirus type 18 E1. Crystal structure, dimerization, and DNA binding. J Biol Chem, 279 (5). pp. 3733-42. ISSN 0021-9258 (Print) (Public Dataset)

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DOI: 10.1074/jbc.M311681200


High risk types of human papillomavirus, such as type 18 (HPV-18), cause cervical carcinoma, one of the most frequent causes of cancer death in women worldwide. DNA replication is one of the central processes in viral maintenance, and the machinery involved is an excellent target for the design of antiviral therapy. The papillomaviral DNA replication initiation protein E1 has origin recognition and ATP-dependent DNA melting and helicase activities, and it consists of a DNA-binding domain and an ATPase/helicase domain. While monomeric in solution, E1 binds DNA as a dimer. Dimerization occurs via an interaction of hydrophobic residues on a single alpha-helix of each monomer. Here we present the crystal structure of the monomeric HPV-18 E1 DNA-binding domain refined to 1.8-A resolution. The structure reveals that the dimerization helix is significantly different from that of bovine papillomavirus type 1 (BPV-1). However, we demonstrate that the analogous residues required for E1 dimerization in BPV-1 and the low risk HPV-11 are also required for HPV-18 E1. We also present evidence that the HPV-18 E1 DNA-binding domain does not share the same nucleotide and amino acid requirements for specific DNA recognition as BPV-1 and HPV-11 E1.

Item Type: Paper
Uncontrolled Keywords: Base Sequence Binding Competitive Blotting Western Crystallography X-Ray DNA/chemistry metabolism DNA-Binding Proteins chemistry Dimerization Glutathione Transferase metabolism Humans Hydrogen Bonding Models, Molecular Molecular Sequence Data Mutagenesis Site-Directed Oncogene Proteins Viral chemistry metabolism Precipitin Tests Protein Binding Protein Conformation Protein Structure Secondary Protein Structure Tertiary Recombinant Fusion Proteins/metabolism Sequence Homology Amino Acid Viral Proteins chemistry
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
organism description > virus > papillomavirus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein structure rendering
Investigative techniques and equipment > x ray crystallography
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
Depositing User: CSHL Librarian
Date: 30 January 2004
Date Deposited: 21 Mar 2012 19:39
Last Modified: 05 Sep 2017 18:52
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