title: Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III.
abstract: The dimeric ring-shaped sliding clamp of E. coli DNA polymerase III (beta subunit, homolog of eukaryotic PCNA) is loaded onto DNA by the clamp loader gamma complex (homolog of eukaryotic Replication Factor C, RFC). The delta subunit of the gamma complex binds to the beta ring and opens it. The crystal structure of a beta:delta complex shows that delta, which is structurally related to the delta' and gamma subunits of the gamma complex, is a molecular wrench that induces or traps a conformational change in beta such that one of its dimer interfaces is destabilized. Structural comparisons and molecular dynamics simulations suggest a spring-loaded mechanism in which the beta ring opens spontaneously once a dimer interface is perturbed by the delta wrench.
authors.affiliation: Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jeruzalmi
authors.forename: O
authors.initials: O
authors.lastname: Yurieva
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: Stewart
authors.forename: M
authors.initials: M
authors.lastname: Hingorani
authors.forename: M
authors.initials: M
authors.lastname: O'Donnell
authors.forename: J
authors.initials: J
authors.lastname: Kuriyan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004258:DNA Polymerase III / Q000737:chemistry* / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
chemical_list: D004269:DNA, Bacterial; D046911:Macromolecular Substances; D021122:Protein Subunits; D004258:DNA Polymerase III