ArticleMolecular cell2009
Linkage-specific avidity defines the lysine 63-linked polyubiquitin-binding preference of rap80.
Article in Molecular cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 219 citations in OpenAlex.
- The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025Review
- Trafficking of K63-polyubiquitin-modified membrane proteins in a macroautophagy-independent pathway is linked to ATG9A.Molecular biology of the cell · 2025Article
- VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.Nature structural & molecular biology · 2024Article
- AlphaFold Ensemble Competition Screens Enable Peptide Binder Design with Single-Residue Sensitivity.ACS chemical biology · 2024Article
- Secondary interactions in ubiquitin-binding domains achieve linkage or substrate specificity.Cell reports · 2024Article
- K48- and K63-linked ubiquitin chain interactome reveals branch- and length-specific ubiquitin interactors.Life science alliance · 2024Article
- Activity-based profiling of cullin-RING E3 networks by conformation-specific probes.Nature chemical biology · 2023Article
- GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage.Nucleic acids research · 2023Article
- RAP80 phase separation at DNA double-strand break promotes BRCA1 recruitment.Nucleic acids research · 2023Article
- Avidity-based biosensors for ubiquitylated PCNA reveal choreography of DNA damage bypass.Science advances · 2023Article
- Ubiquitin Engineering for Interrogating the Ubiquitin-Proteasome System and Novel Therapeutic Strategies.Cells · 2023Review
- Triubiquitin Probes for Identification of Reader and Eraser Proteins of Branched Polyubiquitin Chains.ACS chemical biology · 2023Article
- Activity-based profiling of cullin-RING ligase networks by conformation-specific probes.bioRxiv : the preprint server for biology · 2023Article
- Systematic characterization of Brassica napus UBC13 genes involved in DNA-damage response and K63-linked polyubiquitination.BMC plant biology · 2023Article
- SUMO enhances unfolding of SUMO-polyubiquitin-modified substrates by the Ufd1/Npl4/Cdc48 complex.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma.Biomedicines · 2022Review
- Diagnosing and mitigating method-based avidity artifacts that confound polyubiquitin-binding assays.Biophysical reports · 2021Article
- Two redundant ubiquitin-dependent pathways of BRCA1 localization to DNA damage sites.EMBO reports · 2021Article
- A modular toolbox to generate complex polymeric ubiquitin architectures using orthogonal sortase enzymes.Nature communications · 2021Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Linkage-specific polyubiquitin recognition is thought to make possible the diverse set of functional outcomes associated with ubiquitination. Thus far, mechanistic insight into this selectivity has been largely limited to single domains that preferentially bind to lysine 48-linked polyubiquitin (K48-polyUb) in isolation. Here, we propose a mechanism, linkage-specific avidity, in which multiple ubiquitin-binding domains are arranged in space so that simultaneous, high-affinity interactions are optimum with one polyUb linkage but unfavorable or impossible with other polyUb topologies and monoUb. Our model is human Rap80, which contains tandem ubiquitin interacting motifs (UIMs) that bind to K63-polyUb at DNA double-strand breaks. We show how the sequence between the Rap80 UIMs positions the domains for efficient avid binding across a single K63 linkage, thus defining selectivity. We also demonstrate K48-specific avidity in a different protein, ataxin-3. Using tandem UIMs, we establish the general principles governing polyUb linkage selectivity and affinity in multivalent ubiquitin receptors.
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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.