A snapshot of ubiquitin chain elongation: lysine 48-tetra-ubiquitin slows down ubiquitination
| Autor: | Jordan, Kovacev, Kenneth, Wu, Donald E, Spratt, Robert A, Chong, Chan, Lee, Jaladhi, Nayak, Gary S, Shaw, Zhen-Qiang, Pan |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
SKP Cullin F-Box Protein Ligases
NEDD8 Protein Lysine Peptide Chain Elongation Translational Ubiquitination macromolecular substances environment and public health HEK293 Cells NF-KappaB Inhibitor alpha Protein Synthesis and Degradation Humans I-kappa B Proteins Polyubiquitin Ubiquitins beta Catenin |
| Zdroj: | The Journal of biological chemistry. 289(10) |
| ISSN: | 1083-351X |
| Popis: | We have explored the mechanisms of polyubiquitin chain assembly with reconstituted ubiquitination of IκBα and β-catenin by the Skp1-cullin 1-βTrCP F-box protein (SCF(βTrCP)) E3 ubiquitin (Ub) ligase complex. Competition experiments revealed that SCF(βTrCP) formed a complex with IκBα and that the Nedd8 modified E3-substrate platform engaged in dynamic interactions with the Cdc34 E2 Ub conjugating enzyme for chain elongation. Using "elongation intermediates" containing β-catenin linked with Ub chains of defined length, it was observed that a Lys-48-Ub chain of a length greater than four, but not its Lys-63 linkage counterparts, slowed the rate of additional Ub conjugation. Thus, the Ub chain length and linkage impact kinetic rates of chain elongation. Given that Lys-48-tetra-Ub is packed into compact conformations due to extensive intrachain interactions between Ub subunits, this topology may limit the accessibility of SCF(βTrCP)/Cdc34 to the distal Ub Lys-48 and result in slowed elongation. |
| Databáze: | OpenAIRE |
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