Fig. 4. Alternative conformers of Pol δ holoenzyme.

a Three representative EM 3D classes showing increasing tilting of the PCNA ring relative to the polymerase. The percentage values indicated next to the EM reconstructions correlate with the proportion of particles assigned to the three 3D classes and represent an estimate of the prevalence of each conformation in the data set. b Overlay of the models corresponding to the EM reconstructions shown in a. Inset: close up of the EM map of Class 1 showing the contact between the Pol δ thumb domain and PCNA loops. Residues K931 in the Pol δ loop and D41 in the PCNA loop are labelled. Density of K931 side chain is missing, indicating that K931 participates in a flexible interaction with PCNA. c PCNA interactions with DNA in Class 2. PCNA subunits are shown as cartoons and colored in different shades. DNA is shown as a yellow ribbon. DNA phosphates within a coulombic interaction distance (<6 Å) from PCNA residues are shown as spheres. Interacting phosphates on the template and primer strands are shown in yellow and red, respectively. Phosphates closer than 5 Å are shown with a larger sphere diameter. PCNA interacting residues are shown as sticks and labeled. d Side-view of the processive complex and Class 2 structures aligned using PCNA. The polymerase component is hidden for clarity. PCNA subunits are shown in different shades of blue and the subunit in the foreground is hidden. DNA molecules in the processive and Class 2 complexes are shown as purple and yellow ribbons, respectively. Phosphates interacting with PCNA residues are shown as spheres. Terminal bases of the DNA substrates are labelled.