The cytomegalovirus DNA polymerase subunit UL44 forms a C clamp-shaped dimer

Mol Cell. 2004 Jul 23;15(2):233-44. doi: 10.1016/j.molcel.2004.06.018.

Abstract

The human cytomegalovirus DNA polymerase consists of a catalytic subunit, UL54, and a presumed processivity factor, UL44. We have solved the crystal structure of residues 1-290 of UL44 to 1.85 A resolution by multiwavelength anomalous dispersion. The structure reveals a dimer of UL44 in the shape of a C clamp. Each monomer of UL44 shares its overall fold with other processivity factors, including herpes simplex virus UL42, which is a monomer that binds DNA directly, and the sliding clamp, PCNA, which is a trimer that surrounds DNA, although these proteins share no obvious sequence homology. Analytical ultracentrifugation and gel filtration measurements demonstrated that UL44 also forms a dimer in solution, and substitution of large hydrophobic residues along the homodimer interface with alanine disrupted dimerization and decreased DNA binding. UL44 represents a hybrid processivity factor as it binds DNA directly like UL42, but forms a C clamp that may surround DNA like PCNA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cytomegalovirus / enzymology*
  • DNA, Viral / genetics*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Humans
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Conformation
  • Protein Folding*
  • Protein Subunits
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • DNA, Viral
  • DNA-Binding Proteins
  • ICP36 protein, Cytomegalovirus
  • Proliferating Cell Nuclear Antigen
  • Protein Subunits
  • Viral Proteins

Associated data

  • PDB/1TGL