PXD027349-2

PXD027349 is an original dataset announced via ProteomeXchange.

Title	Chemical Crosslinking of Isotopically Labeled α-Synuclein Reveals Structural Changes and the Interface of Oligomeric Species
Description	Due to its high pharmaceutical relevance, α-synuclein is one of the best studied intrinsically disordered proteins to date. Its structural plasticity reaches from α-helical when bound to membranes through disordered in solution to β-sheet when forming amyloid fibrils. Recently the possible toxicity of membrane bound α-synuclein oligomers has elicited increased interest in the understanding of its membrane bound state. Both the high structural variability in the bound state and the requirement of membranes to elicit structural conversion of α-synuclein into is oligomeric membrane bound state have impeded the determination of a high-resolution oligomeric membrane-bound structure. The use of chemical crosslinking mass spectrometry (XL-MS) in this context leads to a very large set of peptide spectrum matches (PSMs), which do not permit the elucidation of a single, well defined structure based on XL-MS alone. The pattern of PSMs obtained does, however, represent possible links within the ensemble of membrane bound α-synuclein states. Here, we use fully 15N isotopically labeled α-synuclein in 1:1 mixtures with the natural abundance (14N) protein in order to allow distinction between intermolecular and intramolecular crosslinks in α-synuclein oligomers. Information obtained on the main crosslinking regions as well as changes in the observed PSM patterns is then used in conjunction with data obtained from nuclear magnetic resonance (NMR) measurements to develop high-resolution structural models of α-synuclein. We expect that the approach taken here will also prove useful in other highly flexible oligomeric systems.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:56.564.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Markus Hartl
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-15 23:30:57	ID requested
1	2023-04-07 05:58:22	announced
⏵ 2	2023-11-14 08:52:56	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: human, cross-linking mass spectrometry,α-synuclein

Robert Konrat
contact affiliation	Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Austria
contact email	Robert.Konrat@univie.ac.at
lab head
Markus Hartl
contact affiliation	Mass Spectrometry Facility, Max Perutz Labs Vienna, University of Vienna, Vienna Biocenter, Dr.-Bohr-Gasse 7, 1030 Vienna
contact email	markus.hartl@univie.ac.at
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/2023/04/PXD027349

PRIDE project URI

• PRIDE
  1. PXD027349
     1. Label: PRIDE project
     2. Name: Chemical Crosslinking of Isotopically Labeled α-Synuclein Reveals Structural Changes and the Interface of Oligomeric Species