ArticleProceedings of the National Academy of Sciences of the United States of America2016
Saturation scanning of ubiquitin variants reveals a common hot spot for binding to USP2 and USP21.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- ML364 ameliorates NLRP3-induced inflammatory response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Cold Spot SCANNER: Colab Notebook for predicting cold spots in protein-protein interfaces.BMC bioinformatics · 2024Article
- Protein engineering via sequence-performance mapping.Cell systems · 2023Review
- Article
- Ubiquitin variants potently inhibit SARS-CoV-2 PLpro and viral replication via a novel site distal to the protease active site.PLoS pathogens · 2022Article
- Binary combinatorial scanning reveals potent poly-alanine-substituted inhibitors of protein-protein interactions.Communications chemistry · 2022Article
- Cold spots are universal in protein-protein interactions.Protein science : a publication of the Protein Society · 2022Article
- Identification of an autoinhibitory, mitophagy-inducing peptide derived from the transmembrane domain of USP30.Autophagy · 2022Article
- Massively parallel phenotyping of coding variants in cancer with Perturb-seq.Nature biotechnology · 2022Article
- On the Study of Deubiquitinases: Using the Right Tools for the Job.Biomolecules · 2022Review
- Linkage-Specific Synthesis of Di-ubiquitin Probes Enabled by the Incorporation of Unnatural Amino Acid ThzK.Chembiochem : a European journal of chemical biology · 2022Article
- Insights Into the Properties, Biological Functions, and Regulation of USP21.Frontiers in pharmacology · 2022Review
- Climbing Up and Down Binding Landscapes through Deep Mutational Scanning of Three Homologous Protein-Protein Complexes.Journal of the American Chemical Society · 2021Article
- Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy.International journal of molecular sciences · 2021Review
- Quantitative mapping of binding specificity landscapes for homologous targets by using a high-throughput method.The Biochemical journal · 2020Article
- Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond.Pharmacological reviews · 2020Review
- UBB pseudogene 4 encodes functional ubiquitin variants.Nature communications · 2020Article
- Downregulation of ubiquitin-specific protease 2 possesses prognostic and diagnostic value and promotes the clear cell renal cell carcinoma progression.Annals of translational medicine · 2020Article
- Generating quantitative binding landscapes through fractional binding selections combined with deep sequencing and data normalization.Nature communications · 2020Article
- Article
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A detailed understanding of the molecular mechanisms whereby ubiquitin (Ub) recognizes enzymes in the Ub proteasome system is crucial for understanding the biological function of Ub. Many structures of Ub complexes have been solved and, in most cases, reveal a large structural epitope on a common face of the Ub molecule. However, owing to the generally weak nature of these interactions, it has been difficult to map in detail the functional contributions of individual Ub side chains to affinity and specificity. Here we took advantage of Ub variants (Ubvs) that bind tightly to particular Ub-specific proteases (USPs) and used phage display and saturation scanning mutagenesis to comprehensively map functional epitopes within the structural epitopes. We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or "hot spot," consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences. The Ubv core functional epitope contacts residues that are conserved in the human USP family, and thus it is likely important for the interactions of Ub across many family members.
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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 OpenQuestion graph.