PXD059143

PXD059143 is an original dataset announced via ProteomeXchange.

Title	Mass spectrometry analysis of chemically and collisionally dissociated molecular glue- and PROTAC-mediated protein complexes informs on disassembly pathways.
Description	Molecular glues (MG) and proteolysis-targeting chimeras (PROTACs) are used to modulate protein-protein interactions (PPIs), via induced proximity between compounds that have little or no affinity toward each other naturally. They promote either reversible inhibition or selective degradation of a target protein, including ones deemed undruggable by traditional therapeutics. Though native MS (nMS) is capable of analysing multi-protein complexes, the behaviour of these artificially induced compounds in the gas phase is still not fully understood, and the number of publications over the last few years is still rather limited. Here, we studied two MG-induced complexes between mTORFRB and FKBP12, as well as a PROTAC-induced complex between FKBP51 and the von Hippel-Lindau E3 ligase (VHL). Native MS combined with collision-induced dissociation (CID) provided a way of measuring not only the formation of these complexes, but also their dissociation pathways. Both protein complexes seem to eject preferably the centrally-located small (compared to the mass of the proteins) ligand upon CID, rather than dissociating a peripheral subunit, as is often observed for naturally occurring protein complexes. In contrast, chemically-induced dissociation in solution generated complementary data to CID, by disrupting the PPI surface, which resulted in more diverse MS spectra that preserved the stronger interactions in solution.
HostingRepository	PRIDE
AnnounceDate	2025-02-27
AnnouncementXML	Submission_2025-02-27_00:18:08.075.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Edvaldo Maciiel
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Canavalia brasiliensis; NCBI TaxID: 61861;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-22 20:14:17	ID requested
⏵ 1	2025-02-27 00:18:08	announced

10.1021/JASMS.4C00429;

submitter keyword: Native Mass Spectrometry,Molecular glue, Proteolysis-targeting Chimeras, protein complex., Collision-induced dissociation

Prof. Dr. Frederik Lermyte
contact affiliation	Technical University of Darmstadt, Clemens-Schöpf Institute of Organic Chemistry and Biochemistry, Department of Chemistry, Peter-Grünberg-Straße 4, 64287, Darmstadt, Germany.
contact email	frederik.lermyte@tu-darmstadt.de
lab head
Edvaldo Maciiel
contact affiliation	Technical University of Darmstadt
contact email	edvaldovasconcelossm@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059143
     1. Label: PRIDE project
     2. Name: Mass spectrometry analysis of chemically and collisionally dissociated molecular glue- and PROTAC-mediated protein complexes informs on disassembly pathways.