PXD033205

PXD033205 is an original dataset announced via ProteomeXchange.

Title	First direct observation of elongated conformational states in alpha-synuclein upon liquid-liquid phase separation
Description	α-Synuclein (α-syn) is an intrinsically disordered protein (IDP) that undergoes liquid-liquid phase separation (LLPS), fibrillation, and forms insoluble intracellular Lewy’s bodies in neurons, which are the hallmark of Parkinson’s Disease (PD). Neurotoxicity precedes the formation of aggregates and is probably related to LLPS of α-syn in the cell. The molecular mechanisms underlying the early stages of LLPS are still elusive. To obtain structural insights into α-syn upon LLPS, we take advantage of cross-linking/mass spectrometry (XL-MS) and introduced an innovative new approach, termed COMPASS (COMPetitive PAiring StatisticS). COMPASS unravels transient interactions between α-syn molecules in liquid droplets to derive structural information of α-syn upon LLPS. In this work, we show that the conformational ensemble of α-syn shifts towards more elongated conformational states upon LLPS. We obtain insights into the critical initial stages of PD and establish a novel mass spectrometry-based approach that will aid to solve open questions in LLPS structural biology.
HostingRepository	PRIDE
AnnounceDate	2024-03-18
AnnouncementXML	Submission_2024-03-18_09:52:19.048.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniele Ubbiali
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-13 04:41:55	ID requested
⏵ 1	2024-03-18 09:52:19	announced

Ubbiali D, Fratini M, Piersimoni L, Ihling CH, Kipping M, Heilmann I, Iacobucci C, Sinz A, -Synuclein upon Liquid-Liquid Phase Separation. Angew Chem Int Ed Engl, 61(46):e202205726(2022) [pubmed]

10.1002/anie.202205726;

submitter keyword: Cross-linking Mass spectrometry Liquid-liquid phase separation alpha-synuclein

Andrea Sinz
contact affiliation	Department of Pharmaceutical Chemistry & Bioanalytics AG Sinz Institute of Pharmacy, Center for Structural Mass Spectrometry Martin Luther University Halle-Wittenberg Germany
contact email	andrea.sinz@pharmazie.uni-halle.de
lab head
Daniele Ubbiali
contact affiliation	Martin Luther University of Halle-Wittenberg
contact email	dani.ubbiali7@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033205
     1. Label: PRIDE project
     2. Name: First direct observation of elongated conformational states in alpha-synuclein upon liquid-liquid phase separation