The C-terminal domain (CTD) of the τ subunit of the clamp loader (τc) binds to both the DnaB helicase and the DNA polymerase III α subunit (PolIIIα), and determines their relative positions and orientations on the leading and lagging strands. Here, we present a 3.2 Å resolution structure of Thermus aquaticus PolIIIα in complex with τc and a DNA substrate. The structure reveals that the CTD of τc interacts with the CTD of PolIIIα through its C-terminal helix and the adjacent loop. Additionally, in this complex PolIIIα displays an open conformation that includes the reorientations of the oligonucleotide-binding fold and the thumb domain, which may be an indirect result of crystal packing due to the presence of the τc. Nevertheless, the position of the τc on PolIIIα allows us to suggest an approximate model for how the PolIIIα is oriented and positioned on the DnaB helicase.
Bibliographical noteFunding Information:
We thank the staff at ALS beamline 8.2.2 and NSLS beamline X-25. We also thank R.C. Wilmouth and L.S. Lai for helpful discussions and the staff of the CSB core at Yale. B.L. performed experiments and solved the structure. J.Z.L. provided assistance in phase determination. B.L. and T.A.S. wrote the manuscript. This work was supported by both HHMI funding and NIH grant GM57510 to T.A.S.