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PXD049436

PXD049436 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis
DescriptionATGL 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.
HostingRepositoryPRIDE
AnnounceDate2024-03-25
AnnouncementXMLSubmission_2024-03-25_05:34:46.320.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSarah Masser
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-16 14:58:15ID requested
12024-03-14 04:02:58announced
22024-03-25 05:34:47announced2024-03-25: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: Deep Mutagenesis, CIDEC, PLIN5, PLIN1, ATGL, G0S2, CGI-58
Contact List
Ulrich Stelzl
contact affiliationUniversity of Graz, Pharmaceutical Sciences, Pharmaceutical Chemistry
contact emailulrich.stelzl@uni-graz.at
lab head
Sarah Masser
contact affiliationUniversity of Graz, Institute of Pharmaceutical Sciences
contact emailsarah.masser@uni-graz.at
dataset submitter
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Dataset FTP location
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