Structural analysis of the TKB domain of ubiquitin ligase Cbl-b complexed with its small inhibitory peptide, Cblin.

  title={Structural analysis of the TKB domain of ubiquitin ligase Cbl-b complexed with its small inhibitory peptide, Cblin.},
  author={Ayako Ohno and Arisa Ochi and Nobuo Maita and Tatsuya Ueji and Aki Bando and Reiko Nakao and Katsuya Hirasaka and Tomoki Abe and Shigetada Teshima-kondo and Hisao Nemoto and Yuushi Okumura and Akira Higashibata and Sachiko Yano and Hidehito Tochio and Takeshi Nikawa},
  journal={Archives of biochemistry and biophysics},
6 Citations
Ubiquitin ligase Cbl-b and inhibitory Cblin peptides.
In Vitro Ubiquitination Platform Identifies Methyl Ellipticiniums as Ubiquitin Ligase Inhibitors
It is demonstrated that a class of natural product–based alkaloids, known as methyl ellipticiniums (MEs), is capable of inhibiting ubiquitin ligases intracellularly.
Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle
Transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice, indicating that CbR could serve as an alternative treatment for Muscle atrophy.
A Diet Including Red Bell Pepper Juice and Soy Protein Suppress Physiological Markers of Muscle Atrophy in Mice.
Findings suggest that a diet including RBPJ and soy protein suppress gene expressions related with muscle atrophy, and suggest that this condition may be possible to prevent through dietary intervention.


Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase
The crystal structure of Cbl-N is described, both alone and in complex with a phosphopeptide that represents its binding site in ZAP-70, and it is confirmed that the three domains together form an integrated phosphoprotein-recognition module.
Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl
The results present a mechanism for regulation of c-Cbl's activity by autoinhibition and phosphorylation-induced activation, which is required for RTK ubiquitination.
Additional Serine/Threonine Phosphorylation Reduces Binding Affinity but Preserves Interface Topography of Substrate Proteins to the c-Cbl TKB Domain
It is shown that additional phosphorylation significantly reduces the binding affinity between the TKB domain and its target proteins, EGFR and Sprouty2, as compared to peptides bearing a single tyrosine phosphorylated group.
Structural Characterization of a Novel Cbl Phosphotyrosine Recognition Motif in the APS Family of Adapter Proteins*
A novel mode of phosphopeptide interaction is revealed with the Cbl T KB domain, in which N-terminal residues distal to the phosphotyrosine directly contact residues of the four-helix bundle of the TKB domain.
Autoinhibition and phosphorylation-induced activation mechanisms of human cancer and autoimmune disease-related E3 protein Cbl-b
Structural and NMR and small-angle X-ray scattering analyses revealed that the unphosphorylated N-terminal region of Cbl-b forms a compact structure by an intramolecular interaction, which masks the interaction surface of the RING domain with an E2 ubiquitin-conjugating enzyme.
The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides
It is estimated imposing structural constraints onto the backbone and sidechain of the peptide and preorganize it to the bound conformation in solution will yield nearly an order of magnitude improvement in activity.
Structural basis for a novel intrapeptidyl H‐bond and reverse binding of c‐Cbl‐TKB domain substrates
The c‐Cbl tyrosine kinase binding domain (Cbl‐TKB), essentially an ‘embedded’ SH2 domain, has a critical role in targeting proteins for ubiquitination and an obligatory, intrapeptidyl H‐bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orientates the peptide into a positively charged pocket on c‐ Cbl.
Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3
A crystal structure of a monomeric RING E3, Tyr363-phosphorylated human CBL-B, bound to a stabilized Ub-linked E2 is presented, revealing a similar mechanism in activating E2~Ub and proposing that an additional non-RING Ub-priming element may be a common RINGE3 feature.