PDBsum entry 1p22

Signaling protein

PDB id: 1p22

Contents

Protein chains

402 a.a. *

131 a.a. *

11 a.a. *

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of a beta-Trcp1-Skp1-Beta-Catenin complex: destruction motif binding and lysine specificity of the scf(beta-Trcp1) ubiquitin ligase.

Authors

G.Wu, G.Xu, B.A.Schulman, P.D.Jeffrey, J.W.Harper, N.P.Pavletich.

Ref.

Mol Cell, 2003, 11, 1445-1456. [DOI no: 10.1016/S1097-2765(03)00234-X]

PubMed id

12820959

Abstract

The SCF ubiquitin ligases catalyze protein ubiquitination in diverse cellular processes. SCFs bind substrates through the interchangeable F box protein subunit, with the >70 human F box proteins allowing the recognition of a wide range of substrates. The F box protein beta-TrCP1 recognizes the doubly phosphorylated DpSGphiXpS destruction motif, present in beta-catenin and IkappaB, and directs the SCF(beta-TrCP1) to ubiquitinate these proteins at specific lysines. The 3.0 A structure of a beta-TrCP1-Skp1-beta-catenin complex reveals the basis of substrate recognition by the beta-TrCP1 WD40 domain. The structure, together with the previous SCF(Skp2) structure, leads to the model of SCF catalyzing ubiquitination by increasing the effective concentration of the substrate lysine at the E2 active site. The model's prediction that the lysine-destruction motif spacing is a determinant of ubiquitination efficiency is confirmed by measuring ubiquitination rates of mutant beta-catenin peptides, solidifying the model and also providing a mechanistic basis for lysine selection.

Figure 3.
Figure 3. The #-TrCP1-Skp1 Interface Is Similar to that in the Skp1-Skp2 Complex

Figure 5.
Figure 5. The Rate of Ubiquitination by the SCF #-TrCP1 Is Dependent on the Spacing between the Ubiquitination-Site Lysine and the Destruction Motif

The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 11, 1445-1456) copyright 2003.