(A) Side views of the atomic models of Autoinhibited1, the RFC:PCNA crystal structure (Bowman et al., 2004), and of the human RFC:PCNA complex show similarity. (B) Closeup of the nucleotide-binding sites. The cryo-EM map is shown in yellow overlaying the atomic model. The catalytically important Walker A lysine, Walker B glutamates, and trans-acting arginine fingers are shown. The arginine fingers are distant within the active sites of RFC-B,C,D in Autoinhibited1 and 2 and in RFC-B,D of Autoinhibited3, rendering these active sites inactive. For comparison, the nucleotide-binding sites in the atomic model of the RFC:PCNA crystal structure (PDB 1SXJ) are shown. Here, the SRC motif arginine fingers were mutated to glutamines. RFC-E is not catalytically competent and has ADP bound. The A′ domain does not donate trans-acting arginine fingers. (C) Top views on the AAA+ spiral of the T4 clamp loader, RFC:PCNA crystal structure and Autoinihibited1–3. The T4 clamp loader, which has DNA bound, is in an active conformation. Here, the rotation axes that relate the subunits are coincident with each other and the central axis of DNA. In contrast, the symmetry of the AAA+ spiral of RFC in the autoinhibited conformation is distorted, and the axes are skewed in all these structures.