title: The cytomegalovirus DNA polymerase subunit UL44 forms a C clamp-shaped dimer.
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.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Appleton
authors.forename: Arianna
authors.initials: A
authors.lastname: Loregian
authors.forename: David J
authors.initials: DJ
authors.lastname: Filman
authors.forename: Donald M
authors.initials: DM
authors.lastname: Coen
authors.forename: James M
authors.initials: JM
authors.lastname: Hogle
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003587:Cytomegalovirus / Q000201:enzymology*; D004279:DNA, Viral / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D021122:Protein Subunits; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C072217:ICP36 protein, Cytomegalovirus; D018809:Proliferating Cell Nuclear Antigen; D021122:Protein Subunits; D014764:Viral Proteins