PXD024671-1

PXD024671 is an original dataset announced via ProteomeXchange.

Title	The structural heterogeneity of α-synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds
Description	The intrinsically disordered protein, α-synuclein, implicated in synaptic vesicle homeostasis and neurotransmitter release, is also associated with several neurodegenerative diseases. The different roles of α-synuclein are characterized by distinct structural states (membrane-bound, dimer, tetramer, oligomer, and fibril), which are originated from its various monomeric conformations. The pathological states, determined by the ensemble of α-synuclein monomer conformations and dynamic pathways of interconversion between dominant states, remain elusive due to their transient nature. Here, we use inter-dye distance distributions from bulk time-resolved Förster resonance energy transfer as restraints in discrete molecular dynamics simulations to map the conformational space of the α-synuclein monomer. We further confirm the generated conformational ensemble in orthogonal experiments utilizing far-UV circular dichroism and cross-linking mass spectrometry. Single-molecule protein-induced fluorescence enhancement measurements show that within this conformational ensemble, some of the conformations of αsynuclein are surprisingly stable, exhibiting conformational transitions slower than milliseconds. Our comprehensive analysis of the conformational ensemble reveals essential structural properties and potential conformations that promote its various functions in membrane interaction or oligomer and fibril formation.
HostingRepository	PRIDE
AnnounceDate	2022-10-14
AnnouncementXML	Submission_2022-10-13_20:46:44.337.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MoriyaSlavin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-11 02:20:40	ID requested
⏵ 1	2022-10-13 20:46:45	announced
2	2023-11-14 08:05:36	announced	2023-11-14: Updated project metadata.

Chen J, Zaer S, Drori P, Zamel J, Joron K, Kalisman N, Lerner E, Dokholyan NV, -synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds. Structure, 29(9):1048-1064.e6(2021) [pubmed]

submitter keyword: CL-MS,α-Synuclein monomer, trFRET,molecular dynamics.

EitanLerner
contact affiliation	Dept. of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
contact email	Eitan.lerner@mail.huji.ac.il
lab head
MoriyaSlavin
contact affiliation	Biochemistry department in the Hebrew University
contact email	moriya.slavin@mail.huji.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024671
     1. Label: PRIDE project
     2. Name: The structural heterogeneity of α-synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds