The Crystal Structure of an Unusual Processivity Factor, Herpes Simplex Virus UL42, Bound to the C Terminus of Its Cognate Polymerase

Mol Cell. 2000 Feb;5(2):267-78. doi: 10.1016/s1097-2765(00)80422-0.

Abstract

Herpes simplex virus DNA polymerase is a heterodimer composed of a catalytic subunit, Pol, and an unusual processivity subunit, UL42, which, unlike processivity factors such as PCNA, directly binds DNA. The crystal structure of a complex of the C-terminal 36 residues of Pol bound to residues 1-319 of UL42 reveals remarkable similarities between UL42 and PCNA despite contrasting biochemical properties and lack of sequence homology. Moreover, the Pol-UL42 interaction resembles the interaction between the cell cycle regulator p21 and PCNA. The structure and previous data suggest that the UL42 monomer interacts with DNA quite differently than does multimeric toroidal PCNA. The details of the structure lead to a model for the mechanism of UL42, provide the basis for drug design, and allow modeling of other proteins that lack sequence homology with UL42 or PCNA.

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

  • Antiviral Agents
  • Crystallography
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism
  • Drug Design
  • Exodeoxyribonucleases / chemistry*
  • Exodeoxyribonucleases / metabolism
  • Models, Molecular
  • Peptide Fragments / chemistry
  • Proliferating Cell Nuclear Antigen / chemistry
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Binding
  • Simplexvirus*
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • DNA-Binding Proteins
  • Peptide Fragments
  • Proliferating Cell Nuclear Antigen
  • Viral Proteins
  • DNA-Directed DNA Polymerase
  • Exodeoxyribonucleases
  • DNA polymerase, Simplexvirus

Associated data

  • PDB/1DML