PXD049436

PXD049436 is an original dataset announced via ProteomeXchange.

Title	Mutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis
Description	ATGL is the key enzyme in intracellular lipolysis playing a critical role in metabolic and cardiovascular diseases. ATGL is tightly regulated through a known set of protein-protein interaction partners with activating or inhibiting functions in control of lipolysis. However, the binding mode and protein interaction sites of ATGL and its partners are unknown. Using deep mutational protein interaction perturbation scanning we generated comprehensive profiles of single amino acid variants effecting the interactions of ATGL with its regulatory partners: CGI-58, G0S2, PLIN1, PLIN5 and CIDEC. Twenty-three ATGL variants gave a specific interaction perturbation pattern when validated in co-immunoprecipitation experiments in mammalian cells. We identified and characterized eleven, highly selective ATGL “switch” mutations which affect the interaction of one of the five partners without affecting the others. Switch mutations thus provided distinct interaction determinants for ATGL’s key regulatory proteins at an amino acid resolution. When tested for triglyceride hydrolase activity in vitro and lipolysis in cells, the activity patterns of the ATGL switch variants traced to their protein interaction profile. In the context of structural data, the integration of variant binding and activity profiles provided important insights into lipolysis regulation and the impact of mutations in human disease.
HostingRepository	PRIDE
AnnounceDate	2024-03-25
AnnouncementXML	Submission_2024-03-25_05:34:46.320.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sarah Masser
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-16 14:58:15	ID requested
1	2024-03-14 04:02:58	announced
⏵ 2	2024-03-25 05:34:47	announced	2024-03-25: Updated project metadata.

10.1038/s41467-024-46937-x;

Kohlmayr JM, Grabner GF, Nusser A, H, ö, ll A, Manojlovi, ć V, Halwachs B, Masser S, Jany-Luig E, Engelke H, Zimmermann R, Stelzl U, Mutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis. Nat Commun, 15(1):2516(2024) [pubmed]

submitter keyword: Deep Mutagenesis, CIDEC, PLIN5, PLIN1, ATGL, G0S2, CGI-58

Ulrich Stelzl
contact affiliation	University of Graz, Pharmaceutical Sciences, Pharmaceutical Chemistry
contact email	ulrich.stelzl@uni-graz.at
lab head
Sarah Masser
contact affiliation	University of Graz, Institute of Pharmaceutical Sciences
contact email	sarah.masser@uni-graz.at
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/03/PXD049436

PRIDE project URI

• PRIDE
  1. PXD049436
     1. Label: PRIDE project
     2. Name: Mutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis