The five subunits of the clamp loader are referred to as the A, B, C, D, and E subunits, and the AAA+ modules within a complex form a spiral assembly when bound to ATP ( Bowman et al., 2004). The AAA+ module in each subunit is connected to a C-terminal collar domain that is responsible for oligomerization of the clamp loader ( Bowman et al., 2004 Guenther et al., 1997 Jeruzalmi et al., 2001 Figure 1A). Each subunit in a clamp-loader complex contains a two-domain AAA+ module that is characteristic of the AAA+ ATPases. The ATPase subunits of clamp loaders are members of the very large and diverse family of AAA+ ATPases, which are oligomeric proteins that bind and hydrolyze ATP at interfacial sites ( Gates and Martin, 2020 Neuwald et al., 1999). ( C) Key elements of AAA+ modules, shown here at the interface between neighboring ATPase subunits at positions B and C with DNA and the sliding clamp.Īll clamp-loader complexes consist of five subunits that have arisen through gene duplication of an ancestral ATPase subunit.
( B) The clamp loading cycle, from left to right, showing the key stages of loading the sliding clamp around primer-templated DNA. ( A) Crystal structure (left) and schematic diagram (right) of the clamp loader.