PDBsum entry 1axc

Complex (DNA-binding protein/DNA)

PDB id: 1axc

Contents

Protein chains

249 a.a. *

18 a.a. *

Waters ×885

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of the c-Terminal region of p21(waf1/cip1) complexed with human pcna.

Authors

J.M.Gulbis, Z.Kelman, J.Hurwitz, M.O'Donnell, J.Kuriyan.

Ref.

Cell, 1996, 87, 297-306. [DOI no: 10.1016/S0092-8674(00)81347-1]

PubMed id

8861913

Abstract

The crystal structure of the human DNA polymerase delta processivity factor PCNA (proliferating cell nuclear antigen) complexed with a 22 residue peptide derived from the C-terminus of the cell-cycle checkpoint protein p21(WAF1/CIP1) has been determined at 2.6 angstrom resolution. p21 binds to PCNA in a 1:1 stoichiometry with an extensive array of interactions that include the formation of a beta sheet with the interdomain connector loop of PCNA. An intact trimeric ring is maintained in the structure of the p21-PCNA complex, with a central hole available for DNA interaction. The ability of p21 to inhibit the action of PCNA is therefore likely to be due to its masking of elements on PCNA that are required for the binding of other components of the polymerase assembly.

Figure 1.
Figure 1. Ribbon Diagram of the PCNA Monomer with Bound p21 Peptide(a) Stereo diagram of the three-dimensional structure of one monomer of the PCNA–p21 peptide complex, looking directly onto the face of the ring. The peptide (colored red) runs alongside the interdomain connecting loop (green). The N-terminal domain of PCNA is drawn in yellow and the C-terminal domain in plum, with five residues at the terminus shaded blue. Figure prepared using the programs MOLSCRIPT ([21]) and Raster-3D ( [2]).(b) Superimposition of the C^α trace of PCNA from S. cerevisiae (red) onto that of human PCNA (black) with bound p21 peptide (green). The orientation is similar to that in (a). Prepared using the programs O ([16]) and MOLSCRIPT ( [21]).

Figure 3.
Figure 3. Interactions at the p21–PCNA Interface(a) Schematic depiction of contacts between the peptide and PCNA. Residues of the connector loop of PCNA are shaded green, those of the C-terminus are in yellow, and other PCNA residues are in pink. A set of two water-mediated contacts is also shown (blue circles).(b) Hydrophobic interactions at the p21–PCNA interface. A set of four side chains of the p21-peptide (red) fit into hydrophobic cavities in the molecular surface of PCNA. The C^α trace of PCNA is displayed as a green tube. PCNA residues lining the pockets (shown in yellow) are: Cys-27, Met-40, Val-45, Leu-47, Ala-67, Gly-69, Leu-121, Val-123, Leu-126, Ile-128, Pro-129, 133-Tyr, Pro-234, Tyr-250, Ala-252, Pro-253, and (in green) Gln-131, which contacts the hydroxyl of the peptide tyrosine. This figure was generated using GRASP.

The above figures are reprinted by permission from Cell Press: Cell (1996, 87, 297-306) copyright 1996.