Structure of a β-TrCP1-Skp1-β-catenin complex: Destruction motif binding and lysine specificity of the SCFβ-TrCP1 ubiquitin ligase Journal Article
| Authors: | Wu, G.; Xu, G.; Schulman, B. A.; Jeffrey, P. D.; Harper, J. W.; Pavletich, N. P. |
| Article Title: | Structure of a β-TrCP1-Skp1-β-catenin complex: Destruction motif binding and lysine specificity of the SCFβ-TrCP1 ubiquitin ligase |
| 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 β-TrCP1 recognizes the doubly phosphorylated DpSGφXpS destruction motif, present in β-catenin and IκB, and directs the SCFβ-TrCP1 to ubiquitinate these proteins at specific lysines. The 3.0 Å structure of a β-TrCP1-Skp1-β-catenin complex reveals the basis of substrate recognition by the β-TrCP1 WD40 domain. The structure, together with the previous SCFSkp2 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 β-catenin peptides, solidifying the model and also providing a mechanistic basis for lysine selection. |
| Keywords: | mutant protein; ubiquitin; protein conformation; protein domain; protein motif; cell cycle proteins; protein binding; gtp-binding proteins; in vitro study; prediction; amino acid sequence; conserved sequence; molecular sequence data; kinetics; substrate specificity; peptides; crystal structure; models, molecular; crystallography, x-ray; binding sites; trans-activators; catalysis; protein structure; enzyme specificity; beta catenin; isoprotein; lysine; amino acid motifs; s-phase kinase-associated proteins; ligase; cytoskeletal proteins; ligases; peptide derivative; consensus sequence; humans; article; beta-transducin repeat-containing proteins |
| Journal Title: | Molecular Cell |
| Volume: | 11 |
| Issue: | 6 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2003-06-01 |
| Start Page: | 1445 |
| End Page: | 1456 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(03)00234-x |
| PUBMED: | 12820959 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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