PXD048963

PXD048963 is an original dataset announced via ProteomeXchange.

Title	Cobalamins function as allosteric activators of an Angelman syndrome-associated UBE3A/E6AP variant
Description	Genetic 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:38:44.427.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-29 01:37:31	ID requested
1	2024-05-09 15:19:53	announced
⏵ 2	2024-10-22 06:38:45	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: LiP-MS, small molecule activators, qXL-MS, structural proteomics,UBE3A, Angelman syndrome

Prof. Dr. Florian Stengel
contact affiliation	Department of Biology, University of Konstanz, Universitaetsstrasse 10, 78457 Konstanz, Germany
contact email	florian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048963
     1. Label: PRIDE project
     2. Name: Cobalamins function as allosteric activators of an Angelman syndrome-associated UBE3A/E6AP variant