PXD030299

PXD030299 is an original dataset announced via ProteomeXchange.

Title	Integrative structure models of the α-Synuclein dimer conformations
Description	α-Synuclein is an intrinsically disordered protein known for its contributions to functions in neurons but mostly in its contributions to the development of Parkinson's disease via formation of self-associated forms, fibrils and Lewy bodies. Among the multiple targets it interacts with and gains a folded structure within the bound state, are homo-oligomers. Logically, the shortest homo-oligomer a protein can form is a dimer. However, until today the existence of the α-Synuclein dimer has been a subject of much debate. Using an array of measurements, we show that in vitro α-Synuclein exhibits primarily a monomer-dimer equilibrium within a concentration range of hundreds of nanomolars and up to a few micromolars. Furthermore, we performed hetero-isotopic cross-linking mass spectrometry experiments, from which we gained spatial information on the dimer that was then used in constructing restraints for discrete molecular dynamics simulations. This allowed us to retrieve integrative structure models of α-Synuclein dimer structural subpopulations, having different degrees of compactness and binding energies. Interestingly, one of dimers structures is compact, stable, abundant and exhibits partially-exposed β-sheet structures in the N-terminal and non-amyloid component segments. This compact dimer form is also the only one that exhibits interaction distances between hydroxyl groups of tyrosine 39 in the two subunits. We suggest that the high abundance compact dimer form serves as an important α-Synuclein dimeric species and propose different hypotheses as to its function, whether on pathway to aggregation or not
HostingRepository	PRIDE
AnnounceDate	2023-01-30
AnnouncementXML	Submission_2023-01-30_01:46:59.406.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JoannaZamel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-11 15:05:37	ID requested
⏵ 1	2023-01-30 01:46:59	announced

Dataset with its publication pending

submitter keyword: α-Synuclein, dimer,parkinson's,hetreo isotopic CL-MS

EitanLerner
contact affiliation	Dr.Eitan Lerner's lab, The Department of Biological Chemistry The Alexander Silberman Institute for Life Sciences, The Hebrew University of Jerusalem ISRAEL
contact email	eitan.lerner@mail.huji.ac.il
lab head
JoannaZamel
contact affiliation	The Hebrew University of Jerusalem
contact email	joanna.zamel@mail.huji.ac.il
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/2023/01/PXD030299

PRIDE project URI

• PRIDE
  1. PXD030299
     1. Label: PRIDE project
     2. Name: Integrative structure models of the α-Synuclein dimer conformations