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http://purl.uniprot.org/citations/35385646http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35385646http://www.w3.org/2000/01/rdf-schema#comment"Ubiquitin (Ub)-binding domains embedded in intracellular proteins act as readers of the complex Ub code and contribute to regulation of numerous eukaryotic processes. Ub-interacting motifs (UIMs) are short α-helical modular recognition elements whose role in controlling proteostasis and signal transduction has been poorly investigated. Moreover, impaired or aberrant activity of UIM-containing proteins has been implicated in numerous diseases, but targeting modular recognition elements in proteins remains a major challenge. To overcome this limitation, we developed Ub variants (UbVs) that bind to 42 UIMs in the human proteome with high affinity and specificity. Structural analysis of a UbV:UIM complex revealed the molecular determinants of enhanced affinity and specificity. Furthermore, we showed that a UbV targeting a UIM in the cancer-associated Ub-specific protease 28 potently inhibited catalytic activity. Our work demonstrates the versatility of UbVs to target short α-helical Ub receptors with high affinity and specificity. Moreover, the UbVs provide a toolkit to investigate the role of UIMs in regulating and transducing Ub signals and establish a general strategy for the systematic development of probes for Ub-binding domains."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.org/dc/terms/identifier"doi:10.1021/acschembio.2c00089"xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Kurinov I."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Singer A.U."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Sicheri F."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Sidhu S.S."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Manczyk N."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Veggiani G."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Yates B.P."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/author"Martyn G.D."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/name"ACS Chem Biol"xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/pages"941-956"xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/title"Panel of Engineered Ubiquitin Variants Targeting the Family of Human Ubiquitin Interacting Motifs."xsd:string
http://purl.uniprot.org/citations/35385646http://purl.uniprot.org/core/volume"17"xsd:string
http://purl.uniprot.org/citations/35385646http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35385646
http://purl.uniprot.org/citations/35385646http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35385646
http://purl.uniprot.org/uniprot/#_P0CG47-mappedCitation-35385646http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35385646
http://purl.uniprot.org/uniprot/#_Q6ZTN6-mappedCitation-35385646http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35385646
http://purl.uniprot.org/uniprot/P0CG47http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/35385646
http://purl.uniprot.org/uniprot/Q6ZTN6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/35385646