Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III

The 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.