1P22

Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity on the SCFbeta-TrCP1 ubiquitin ligase

Summary for 1P22

• Entry DOI: 10.2210/pdb1p22/pdb
• Descriptor: F-box/WD-repeat protein 1A, Skp1, Beta-catenin (3 entities in total)
• Functional Keywords: ubiquitination, degradation, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9Y297 P35222
• Total number of polymer chains: 3
• Total formula weight: 69195.61

Authors

Wu, G.,Xu, G.,Schulman, B.A.,Jeffrey, P.D.,Harper, J.W.,Pavletich, N.P. (deposition date: 2003-04-14, release date: 2003-07-08, Last modification date: 2024-10-30)

Primary citation

Wu, G.,Xu, G.,Schulman, B.A.,Jeffrey, P.D.,Harper, J.W.,Pavletich, N.P.
Structure of a beta-TrCP1-Skp1-beta-Catenin complex: destruction motif binding and lysine specificity of the SCFbeta-TrCP1 ubiquitin ligase
Mol.Cell, 11:1445-1456, 2003

PubMed 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.

PubMed: 12820959
DOI: 10.1016/S1097-2765(03)00234-X

Experimental method

X-RAY DIFFRACTION (2.95 Å)