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PXD024671

PXD024671 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe structural heterogeneity of α-synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2022-10-14
AnnouncementXMLSubmission_2022-10-13_20:46:44.337.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMoriyaSlavin
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-11 02:20:40ID requested
12022-10-13 20:46:45announced
Publication List
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]
Keyword List
submitter keyword: CL-MS,α-Synuclein monomer, trFRET,molecular dynamics.
Contact List
EitanLerner
contact affiliationDept. of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
contact emailEitan.lerner@mail.huji.ac.il
lab head
MoriyaSlavin
contact affiliationBiochemistry department in the Hebrew University
contact emailmoriya.slavin@mail.huji.ac.il
dataset submitter
Full Dataset Link List
Dataset FTP location
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