Structure of PCNA free and bound to p21 PIP-box peptides.

(A) Ribbon scheme of the crystal structure of human PCNA trimeric ring (PDB entry 1VYM) front and side views showing the three protomers in different colors. The IDCL (residues 117–134), the βD2−βE2 loop (184–195), the βH1−βI1 (residues 105–109) and the C-terminus are labeled on the protomer colored in green. The five C-terminal residues (residues 256–261) not seen in the crystal structure are indicated by circles in the same protomer. (B) Ribbon representation of the crystal structure of one of the PCNA protomers bound to the p21²² peptide (PDB entry 1AXC) and the CSPs caused by p21²⁰ peptide binding in solution. The short αA helix of the p21²² peptide docks into a hydrophobic pocket partly formed by the C-terminal half of the IDCL of PCNA, while the peptide βB strand interacts mostly with the extended N-terminal half of the IDCL. The residues not seen in the crystal are indicated by circles. The p21 residues in common with both the p21¹² and p21²⁰ peptides are colored in purple, the ones in common only with the p21²⁰ peptide in cyan, and the two N-terminal residues not present in any of these two peptides are colored in light blue. The labels indicate the IDCL, two loops with missing residues in the crystal and the C-terminus of PCNA and the secondary structural elements of the p21²² peptide. Those PCNA residues that experience CSPs larger than the average (0.057 ppm), or larger than the average plus one standard deviation (0.152 ppm), are colored in orange and in magenta, respectively. Except for the IDCL, the loops are labeled using the original nomenclature, indicating with a greek letter the types of secondary structure elements connected by the loop, with a capital latin letter the order of those elements along the PCNA sequence, and with a number the corresponding pseudodomain of the PCNA protomer [14]. This figure was prepared with the program PyMol (Schrödinger).