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

David Jeruzalmi, Olga Yurieva, Yanxiang Zhao, Matthew Young, Jelena Stewart,
Manju Hingorani, Mike O'Donnell and John Kuriyan

Cell, Vol 106, 417-428, August 2001

Summary

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 delta :beta complex shows that delta , which is structurally related to the delta-prime 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.

The schematic drawing below shows the gamma complex at a bacterial replication fork, attached to the two polymerase subunits of the DNA polymerase III holoenzyme. The gamma complex is shown in the act of loading a new sliding clamp (yellow) onto a newly primed piece of DNA