PXD058124

PXD058124 is an original dataset announced via ProteomeXchange.

Title	Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies (Part 1)
Description	The aggregation of the protein alpha-synuclein (αSyn) is a common feature of multiple neurodegenerative diseases collectively called synucleinopathies, for which the pathobiology is not well understood. The different phenotypic characteristics of the synucleinopathies Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System atrophy (MSA) have been proposed to originate from the distinct structures adopted by αSyn in its amyloid forms. Here, using covalent labeling and limited proteolysis coupled to mass spectrometry (LiP-MS) in vitro and in situ within neuronal cells and directly in native patient brain homogenates, we show that pathogenic αSyn from distinct synucleinopathies (PD, DLB and MSA) are structurally different. Further, we found that fibrillar structural differences are associated with different fibril interactomes and neuronal responses. We discovered disease-specific ubiquitination patterns and turnover profiles for pathogenic αSyn species, detected molecular pathways responding specifically to the uptake of different αSyn fibrillar polymorphs, and identified a subset of the involved proteins as candidate direct interactors of αSyn. LiP-MS also identified sets of proteins with altered protease susceptibility in postmortem brain homogenates of PD, DLB, and MSA patients. These sets were largely disease-specific and included proteins altered in cells treated with fibrils derived from patients with the matching disease. Data included in this PRIDE submission concern covalent labeling coupled to mass spectrometry in vitro (Part 1 of this work). Other data are available in separate PRIDE submissions with the same title (Part 2).
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_16:16:41.285.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD058124
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Virginie Redeker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	biotinylated residue; monohydroxylated residue
Instrument	TripleTOF 4600

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-21 01:16:56	ID requested
⏵ 1	2026-06-07 16:16:42	announced

10.1038/s44320-026-00199-5;

Serdiuk T, Redeker V, Savistchenko J, Neupane S, Haenseler W, Fleischmann Y, Reber V, Keller S, Tiberi C, Bachmann-Gagescu R, Gstaiger M, Braun T, Riek R, Gentleman S, Aguzzi A, de Souza N, Melki R, Picotti P, Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies. Mol Syst Biol, 22(6):868-901(2026) [pubmed]

10.6019/PXD058124;

submitter keyword: synucleopathies,Structural proteomics

mass spectrometry

chemical surface modification

NHS-Biotin

nanoLC-MSMS, amplified synuclein fibrils

Virginie REDEKER
contact affiliation	MIRCen, CNRS UMR 9199, Fontenay-aux-Roses, France
contact email	virginie.redeker@cnrs.fr
lab head
Virginie Redeker
contact affiliation	CNRS
contact email	virginie.redeker@cnrs.fr
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/2026/06/PXD058124

PRIDE project URI

• PRIDE
  1. PXD058124
     1. Label: PRIDE project
     2. Name: Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies (Part 1)