Structural dynamics of the E6AP/UBE3A-E6-p53 enzyme-substrate complex

Cite This

Files in this item

Checksum: MD5:d0c8a5a9b76b7b13a730a2f5e3c21ac0

SAILER, Carolin, Fabian OFFENSPERGER, Alexandra JULIER, Kai-Michael KAMMER, Ryan WALKER-GRAY, Matthew G. GOLD, Martin SCHEFFNER, Florian STENGEL, 2018. Structural dynamics of the E6AP/UBE3A-E6-p53 enzyme-substrate complex. In: Nature communications. 9, 4441. eISSN 2041-1723. Available under: doi: 10.1038/s41467-018-06953-0

@article{Sailer2018-10-25Struc-43853, title={Structural dynamics of the E6AP/UBE3A-E6-p53 enzyme-substrate complex}, year={2018}, doi={10.1038/s41467-018-06953-0}, volume={9}, journal={Nature communications}, author={Sailer, Carolin and Offensperger, Fabian and Julier, Alexandra and Kammer, Kai-Michael and Walker-Gray, Ryan and Gold, Matthew G. and Scheffner, Martin and Stengel, Florian}, note={Article Number: 4441} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/43853"> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/43853/1/Sailer_2-1vaz50c6yli0r0.pdf"/> <dc:contributor>Offensperger, Fabian</dc:contributor> <dc:contributor>Sailer, Carolin</dc:contributor> <dc:creator>Sailer, Carolin</dc:creator> <dc:creator>Offensperger, Fabian</dc:creator> <dc:contributor>Julier, Alexandra</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:abstract xml:lang="eng">Deregulation of the ubiquitin ligase E6AP is causally linked to the development of human disease, including cervical cancer. In complex with the E6 oncoprotein of human papillomaviruses, E6AP targets the tumor suppressor p53 for degradation, thereby contributing to carcinogenesis. Moreover, E6 acts as a potent activator of E6AP by a yet unknown mechanism. However, structural information explaining how the E6AP-E6-p53 enzyme-substrate complex is assembled, and how E6 stimulates E6AP, is largely missing. Here, we develop and apply different crosslinking mass spectrometry-based approaches to study the E6AP-E6-p53 interplay. We show that binding of E6 induces conformational rearrangements in E6AP, thereby positioning E6 and p53 in the immediate vicinity of the catalytic center of E6AP. Our data provide structural and functional insights into the dynamics of the full-length E6AP-E6-p53 enzyme-substrate complex, demonstrating how E6 can stimulate the ubiquitin ligase activity of E6AP while facilitating ubiquitin transfer from E6AP onto p53.</dcterms:abstract> <dc:creator>Kammer, Kai-Michael</dc:creator> <dc:contributor>Gold, Matthew G.</dc:contributor> <dc:contributor>Kammer, Kai-Michael</dc:contributor> <dc:contributor>Scheffner, Martin</dc:contributor> <dc:creator>Julier, Alexandra</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/43853/1/Sailer_2-1vaz50c6yli0r0.pdf"/> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>Gold, Matthew G.</dc:creator> <dc:contributor>Walker-Gray, Ryan</dc:contributor> <dc:rights>terms-of-use</dc:rights> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-11-15T13:41:13Z</dc:date> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-11-15T13:41:13Z</dcterms:available> <dc:contributor>Stengel, Florian</dc:contributor> <dc:creator>Scheffner, Martin</dc:creator> <dc:language>eng</dc:language> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/43853"/> <dcterms:rights rdf:resource="https://kops.uni-konstanz.de/page/termsofuse"/> <dcterms:issued>2018-10-25</dcterms:issued> <dc:creator>Stengel, Florian</dc:creator> <dcterms:title>Structural dynamics of the E6AP/UBE3A-E6-p53 enzyme-substrate complex</dcterms:title> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:creator>Walker-Gray, Ryan</dc:creator> </rdf:Description> </rdf:RDF>

Downloads since Nov 15, 2018 (Information about access statistics)

Sailer_2-1vaz50c6yli0r0.pdf 35

This item appears in the following Collection(s)

Search KOPS


Browse

My Account