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PXD062122

PXD062122 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMechanism of D-type cyclins recognition by the AMBRA1 E3 ligase receptor
DescriptionAMBRA1 is a tumour suppressor protein that functions as a substrate receptor in the ubiquitin conjugation system and regulates the stability of D-type cyclins and cell proliferation. Here, we present the cryo-EM structure of cyclin D1 bound AMBRA1-DDB1 complex at 3.55 Å resolution. The structure reveals a substrate interaction surface on the AMBRA1 WD40 domain that specifically binds to the C-terminal region of D-type cyclins. This interaction is dependent on the phosphorylation of Thr286 residue in the C-terminal phosphodegron site of D-type cyclins. The phosphodegron motif folds into a turn-like conformation followed by a 310 helix that promotes its assembly with AMBRA1. Additionally, we show that AMBRA1 mutants, which are defective in cyclin D1 binding, lead to cyclin D1 accumulation and DNA damage. Understanding the AMBRA1-D-type cyclins structure enhances the knowledge of the molecular mechanisms that govern the cell cycle control and may lead to new therapeutic approaches for cancers linked to abnormal cyclin D activity.
HostingRepositoryPRIDE
AnnounceDate2025-04-17
AnnouncementXMLSubmission_2025-04-16_17:46:42.455.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGoran Stjepanovic
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-03-21 08:21:16ID requested
12025-04-16 17:46:42announced
Publication List
10.1126/SCIADV.ADU8708;
Keyword List
submitter keyword: E3 ligase, cyclin D1,AMBRA1
Contact List
Goran Stjepanovic
contact affiliationKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China.
contact emailgoranstjepanovic@cuhk.edu.cn
lab head
Goran Stjepanovic
contact affiliationCUHKSZ
contact emailgoranstjepanovic@cuhk.edu.cn
dataset submitter
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