Pivotal role for the ubiquitin Y59-E51 loop in lysine 48 polyubiquitination
Copyright policy )Pivotal role for the ubiquitin Y59-E51 loop in lysine 48 polyubiquitination
Significance Our identification and characterization of the ubiquitin (Ub) Y59-E51 loop have uncovered a pivotal determinant for lysine 48 (K48) linkage-specific Ub chain synthesis catalyzed by Cdc34 E2 Ub-conjugating enzyme. The Ub Y59-E51 loop appears to anchor a Cdc34 E2-engaging zone, allowing the landing of E2 and enabling it to gain access to the receptor K48. These findings will provide a strong starting point for future biochemical and structural studies aiming to elucidate the detailed interactions between Ub and E2/E3 enzymes that produce the K48 linkage. In addition, the observed global impact of the Ub Y59-E51 loop in cellular K48-polyubiquitination and apoptosis will stimulate investigations for exploring new therapeutic strategies to induce cell killing through pharmacological perturbation of K48-polyubiquitination.
- The University of Texas Southwestern Medical Center United States
- University of California, San Francisco United States
- Howard Hughes Medical Institute United States
- Icahn School of Medicine at Mount Sinai United States
- University of California, Irvine United States
E2 ubiquitin-conjugating enzyme, Models, Molecular, Protein Structure, Secondary, Magnetic Resonance Spectroscopy, Immunoblotting, Molecular Sequence Data, Apoptosis, Protein Structure, Secondary, Cell Line, Models, receptor ubiquitin, Cell Line, Tumor, Humans, Amino Acid Sequence, Polyubiquitin, Tumor, SKP Cullin F-Box Protein Ligases, Ubiquitin, Lysine, Ubiquitination, Molecular, Hydrogen Bonding, Biological Sciences, Protein Structure, Tertiary, HEK293 Cells, E3 ubiquitin ligase, Amino Acid Substitution, Ubiquitin-Conjugating Enzymes, Mutation, Biocatalysis, RNA Interference, Biochemistry and Cell Biology, Generic health relevance, Tertiary, Protein Binding
E2 ubiquitin-conjugating enzyme, Models, Molecular, Protein Structure, Secondary, Magnetic Resonance Spectroscopy, Immunoblotting, Molecular Sequence Data, Apoptosis, Protein Structure, Secondary, Cell Line, Models, receptor ubiquitin, Cell Line, Tumor, Humans, Amino Acid Sequence, Polyubiquitin, Tumor, SKP Cullin F-Box Protein Ligases, Ubiquitin, Lysine, Ubiquitination, Molecular, Hydrogen Bonding, Biological Sciences, Protein Structure, Tertiary, HEK293 Cells, E3 ubiquitin ligase, Amino Acid Substitution, Ubiquitin-Conjugating Enzymes, Mutation, Biocatalysis, RNA Interference, Biochemistry and Cell Biology, Generic health relevance, Tertiary, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).26 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!