ArticleThe Journal of biological chemistry2013
Multimodal mechanism of action for the Cdc34 acidic loop: a case study for why ubiquitin-conjugating enzymes have loops and tails.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.Molecular cell · 2024Article
- Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases.Nature structural & molecular biology · 2024Article
- Functional conservation and divergence of the helix-turn-helix motif of E2 ubiquitin-conjugating enzymes.The EMBO journal · 2022Article
- Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis.Annual review of biochemistry · 2021Review
- Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler.Nature chemical biology · 2021Article
- Coupled monoubiquitylation of the co-E3 ligase DCNL1 by Ariadne-RBR E3 ubiquitin ligases promotes cullin-RING ligase complex remodeling.The Journal of biological chemistry · 2019Article
- Enzymatic Logic of Ubiquitin Chain Assembly.Frontiers in physiology · 2019Review
- Mechanism and disease association of E2-conjugating enzymes: lessons from UBE2T and UBE2L3.The Biochemical journal · 2016Review
- Mechanism of Lysine 48 Selectivity during Polyubiquitin Chain Formation by the Ube2R1/2 Ubiquitin-Conjugating Enzyme.Molecular and cellular biology · 2016Article
- E2 enzymes: more than just middle men.Cell research · 2016Review
- The molecular basis of lysine 48 ubiquitin chain synthesis by Ube2K.Scientific reports · 2015Article
- Ubiquitin-conjugating enzyme Cdc34 and ubiquitin ligase Skp1-cullin-F-box ligase (SCF) interact through multiple conformations.The Journal of biological chemistry · 2015Article
- Article
- Pivotal role for the ubiquitin Y59-E51 loop in lysine 48 polyubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Inhibitors of the Cdc34 acidic loop: A computational investigation integrating molecular dynamics, virtual screening and docking approaches.FEBS open bio · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Together with ubiquitin ligases (E3), ubiquitin-conjugating enzymes (E2) are charged with the essential task of synthesizing ubiquitin chains onto protein substrates. Some 75% of the known E2s in the human proteome contain unique insertions in their primary sequences, yet it is largely unclear what effect these insertions impart on the ubiquitination reaction. Cdc34 is an important E2 with prominent roles in cell cycle regulation and signal transduction. The amino acid sequence of Cdc34 contains an insertion distal to the active site that is absent in most other E2s, yet this acidic loop (named for its four invariably conserved acidic residues) is critical for Cdc34 function both in vitro and in vivo. Here we have investigated how the acidic loop in human Cdc34 promotes ubiquitination, identifying two key molecular events during which the acidic loop exerts its influence. First, the acidic loop promotes the interaction between Cdc34 and its ubiquitin ligase partner, SCF. Second, two glutamic acid residues located on the distal side of the loop collaborate with an invariably conserved histidine on the proximal side of the loop to suppress the pKa of an ionizing species on ubiquitin or Cdc34 which greatly contributes to Cdc34 catalysis. These results demonstrate that insertions can guide E2s to their physiologically relevant ubiquitin ligases as well as provide essential modalities that promote catalysis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.