PXD062122

PXD062122 is an original dataset announced via ProteomeXchange.

Title	Mechanism of D-type cyclins recognition by the AMBRA1 E3 ligase receptor
Description	AMBRA1 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.
HostingRepository	PRIDE
AnnounceDate	2025-04-17
AnnouncementXML	Submission_2025-04-16_17:46:42.455.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Goran Stjepanovic
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-21 08:21:16	ID requested
⏵ 1	2025-04-16 17:46:42	announced

10.1126/SCIADV.ADU8708;

submitter keyword: E3 ligase, cyclin D1,AMBRA1

Goran Stjepanovic
contact affiliation	Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China.
contact email	goranstjepanovic@cuhk.edu.cn
lab head
Goran Stjepanovic
contact affiliation	CUHKSZ
contact email	goranstjepanovic@cuhk.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062122
     1. Label: PRIDE project
     2. Name: Mechanism of D-type cyclins recognition by the AMBRA1 E3 ligase receptor