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PXD048963

PXD048963 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCobalamins function as allosteric activators of an Angelman syndrome-associated UBE3A/E6AP variant
DescriptionGenetic aberrations of the maternal UBE3A allele, which encodes the E3 ubiquitin ligase E6AP, are the cause of Angelman syndrome (AS), an imprinting disorder. In most cases, the maternal UBE3A allele is not expressed. Yet, approximately 10 percent of AS individuals harbor distinct point mutations in the maternal allele resulting in the expression of full-length E6AP variants that frequently display compromised ligase activity. In a high-throughput screen, we identified cyanocobalamin, a vitamin B12-derivative, and several alloxazine derivatives as activators of the AS-linked E6AP-F583S variant. Furthermore, we show by cross-linking coupled to mass spectrometry that cobalamins affect the structural dynamics of E6AP-F583S and apply limited proteolysis coupled to mass spectrometry to obtain information about the regions of E6AP that are involved in, or are affected by, binding cobalamins and alloxazine derivatives. Our data suggest that dietary supplementation with vitamin B12 could be beneficial for AS individuals.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:38:44.427.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFlorian Stengel
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF; Orbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-29 01:37:31ID requested
12024-05-09 15:19:53announced
22024-10-22 06:38:45announced2024-10-22: Updated project metadata.
Publication List
10.1002/cbic.202400184;
M, ü, ller F, Jansen J, Offensperger F, Eichbichler D, Stengel F, Scheffner M, Cobalamins Function as Allosteric Activators of an Angelman Syndrome-Associated UBE3A/E6AP Variant. Chembiochem, 25(10):e202400184(2024) [pubmed]
Keyword List
submitter keyword: LiP-MS, small molecule activators, qXL-MS, structural proteomics,UBE3A, Angelman syndrome
Contact List
Prof. Dr. Florian Stengel
contact affiliationDepartment of Biology, University of Konstanz, Universitaetsstrasse 10, 78457 Konstanz, Germany
contact emailflorian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliationUniversität Konstanz
contact emailflorian.stengel@uni-konstanz.de
dataset submitter
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Dataset FTP location
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