Mechanism of Processivity Clamp Opening by the Delta Subunit Wrench of the Clamp Loader Complex of E. coli DNA Polymerase III

AbstractThe dimeric ring-shaped sliding clamp of E. coli DNA polymerase III (β subunit, homolog of eukaryotic PCNA) is loaded onto DNA by the clamp loader γ complex (homolog of eukaryotic Replication Factor C, RFC). The δ subunit of the γ complex binds to the β ring and opens it. The crystal structure of a β:δ complex shows that δ, which is structurally related to the δ′ and γ subunits of the γ complex, is a molecular wrench that induces or traps a conformational change in β such that one of its dimer interfaces is destabilized. Structural comparisons and molecular dynamics simulations suggest a spring-loaded mechanism in which the β ring opens spontaneously once a dimer interface is perturbed by the δ wrench