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PXD005509

PXD005509 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhase separation of C9orf72 dipeptide repeats perturbs stress granule metabolism
DescriptionLiquid-liquid phase separation (LLPS) of RNA binding proteins underlies the formation of multiple membraneless organelles involved in RNA metabolism, including stress granules. Defects in stress granule homeostasis constitute a corner stone of ALS/FTLD pathogenesis. Phase separation of ALS-linked stress granule proteins has been shown to rely on hydrophobic interactions. Here we identify an active role for arginine-rich domains in these phase separations. Moreover, arginine-rich dipeptide repeats (DPRs) derived from C9orf72 hexanucleotide repeat expansions similarly undergo LLPS, and induce phase separation of a large set of proteins involved in RNA and stress granule metabolism. In the present proteomics experiment, we wondered which cellular proteins could interact with synthetic PR30 peptide. We took soluble HeLa cell lysate, to which we added increasing concentrations of PR30. The PR30 peptide spontaneously demixed, and could be separated from the solution by gentle centrifugation. Unexpectedly, the resulting pellet was largely resistant to washing steps, suggesting that PR induced the precipitation of different cellular proteins to the insoluble fraction. To see whether weak interactions could still be involved in the process, we also performed mild crosslinking with paraformaldehyde. Mass-spectroscopy (MS) analysis on both crosslinked and uncrosslinked samples identified 874 proteins that were detected and quantified in both conditions.
HostingRepositoryPRIDE
AnnounceDate2017-04-26
AnnouncementXMLSubmission_2017-04-26_04:22:36.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterImpens Francis
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-12-06 06:53:19ID requested
12017-04-26 04:22:37announced
Publication List
Boeynaems S, Bogaert E, Kovacs D, Konijnenberg A, Timmerman E, Volkov A, Guharoy M, De Decker M, Jaspers T, Ryan VH, Janke AM, Baatsen P, Vercruysse T, Kolaitis RM, Daelemans D, Taylor JP, Kedersha N, Anderson P, Impens F, Sobott F, Schymkowitz J, Rousseau F, Fawzi NL, Robberecht W, Van Damme P, Tompa P, Van Den Bosch L, Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics. Mol Cell, 65(6):1044-1055.e5(2017) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: Liquid-liquid phase separation, stress granules, arginine-rich dipeptide repeats, labelfree shotgun proteomics
Contact List
Ludo Van Den Bosch
contact affiliationKU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), 3000 Leuven, Belgium VIB, Vesalius Research Center, Laboratory of Neurobiology, 3000 Leuven, Belgium
contact emailludo.vandenbosch@vib-kuleuven.be
lab head
Impens Francis
contact affiliationVIB Proteomics Expertise Center
contact emailfrancis.impens@vib-ugent.be
dataset submitter
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