Crystal structure of the DNA binding domain of the replication initiation protein E1 from papillomavirus

Mol Cell. 2000 Jul;6(1):149-58.

Abstract

Papillomaviral infection causes both benign and malignant lesions and is a necessary cause of cervical carcinoma. Replication of this virus requires the replication initiation proteins E1 and E2, which bind cooperatively at the origin of replication (ori) as an (E1)2-(E2)2-DNA complex. This is a precursor to larger E1 complexes that distort and unwind the ori. We present the crystal structure of the E1 DNA binding domain refined to 1.9 A resolution. Residues critical for DNA binding are located on an extended loop and an alpha helix. We identify the E1 dimerization surface by selective mutations at an E1/E1 interface observed in the crystal and propose a model for the (E1)2-DNA complex. These and other observations suggest how the E1 DNA binding domain orchestrates assembly of the hexameric helicase on the ori.

Publication types

  • 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
  • Animals
  • Bovine papillomavirus 1 / chemistry*
  • Bovine papillomavirus 1 / genetics
  • Bovine papillomavirus 1 / metabolism
  • Cattle
  • DNA Replication
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Dimerization
  • Female
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Papillomaviridae / pathogenicity
  • Papillomavirus Infections / etiology
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Static Electricity
  • Tumor Virus Infections / etiology
  • Uterine Cervical Neoplasms / etiology
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics

Substances

  • DNA-Binding Proteins
  • E1 protein, Bovine papillomavirus
  • Viral Proteins

Associated data

  • PDB/1F08