ArticleNature structural & molecular biology2023
Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C).
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 17 citations in OpenAlex.
- PCIPG2.0: multi-omics fusion and structure-aware graph autoencoding for protein complex identification.Bioinformatics (Oxford, England) · 2026Article
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- Deep learning-driven decoding of ubiquitination: from regulatory mechanisms to targeted protein degradation.Biology direct · 2026Review
- The APC/C subunit APC7 promotes hepatocellular carcinoma progression by mediating ubiquitination and degradation of LATS1 to activate YAP/TAZ.Biology direct · 2026Article
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- Mechanistic snapshots of lipid-linked sugar transfer.Nature communications · 2025Article
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- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Freeze frame: cracking molecular motion.Nature · 2025Article
- Illuminating ubiquitination mechanisms: How cryo-EM has shed light on Cullin RING E3 ligase function.Current opinion in structural biology · 2025Review
- APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.Nature communications · 2025Article
- Conformational landscapes of a class I ribonucleotide reductase complex during turnover reveal intrinsic dynamics and asymmetry.Nature communications · 2025Article
- [High expression of UBE2S promotes progression of hepatocellular carcinoma by increasing cancer cell stemness].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators.PLoS biology · 2020Article
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Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight has thus far required artificially trapped structures to stabilize specific steps along the enzymatic process. So far, how any ubiquitin ligase builds a proteasomal degradation signal, which is canonically regarded as four or more ubiquitins, remains unclear. Here we present time-resolved cryogenic electron microscopy studies of the 1.2 MDa E3 ubiquitin ligase, known as the anaphase-promoting complex/cyclosome (APC/C), and its E2 co-enzymes (UBE2C/UBCH10 and UBE2S) during substrate polyubiquitination. Using cryoDRGN (Deep Reconstructing Generative Networks), a neural network-based approach, we reconstruct the conformational changes undergone by the human APC/C during polyubiquitination, directly visualize an active E3-E2 pair modifying its substrate, and identify unexpected interactions between multiple ubiquitins with parts of the APC/C machinery, including its coactivator CDH1. Together, we demonstrate how modification of substrates with nascent ubiquitin chains helps to potentiate processive substrate polyubiquitination, allowing us to model how a ubiquitin ligase builds a proteasomal degradation signal.
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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 Socratic graph.