PXD039784

PXD039784 is an original dataset announced via ProteomeXchange.

Title	Detection of structure-specific protein–protein interactions of alpha-synuclein
Description	Parkinson’s disease (PD) is a neurodegenerative disorder associated with the accumulation of intraneuronal protein aggregates called Lewy bodies. These inclusions contain aberrantly folded and aggregated alpha-synuclein (aSyn), a key protein involved in the pathology of PD, for which the mechanisms of toxicity are still largely unknown. Recent studies suggest that the conformational changes occurring during aSyn aggregation process can be expected to lead to alterations in the interactome of aSyn. Therefore, identifying changes in the interactome of monomeric and aggregated states of aSyn could help to understand the underlying molecular mechanisms of PD. Despite substantial efforts, current interactomics approaches do not enable determining structure-specific PPIs and their interaction interfaces on a proteome-wide scale. To address this limitation, we here applied the structural proteomics method limited proteolysis–mass spectrometry to systematically identify structure-specific PPIs of aSyn by probing protein structural alterations within cellular extracts upon treatment with monomeric and aggregated, fibrillar states of aSyn. Overall, we identified several previously known interactors of both monomeric and aggregated aSyn as well as novel putative structure-specific interactors including their interaction interfaces and protein binding parameters in situ. These results may constitute an important step in the understanding of how distinct structural states of disease-associated proteins are involved in disease mechanisms.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:29:04.165.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aleš Holfeld
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-01 05:33:20	ID requested
1	2024-02-10 16:54:04	announced
⏵ 2	2024-10-22 06:29:04	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Amyloid fibrils, Neurodegeneration, Structural proteomics, Protein-protein interactions, LC-MSMS, Alpha-synuclein, Interactome, Induced pluripotent stem cell-derived cortical neurons, Mass spectrometry,Limited proteolysis, Parkinson’s disease, Proteomics, Structure-specific interactions

Paola Picotti
contact affiliation	Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland
contact email	picotti@imsb.biol.ethz.ch
lab head
Aleš Holfeld
contact affiliation	Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland
contact email	holfeld@imsb.biol.ethz.ch
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/2024/02/PXD039784

PRIDE project URI

• PRIDE
  1. PXD039784
     1. Label: PRIDE project
     2. Name: Detection of structure-specific protein–protein interactions of alpha-synuclein