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PXD021115

PXD021115 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHspB8 controls molecular aging of FUS condensates by domain-specific protein interactions Part 2
DescriptionBiomolecular condensates formed by phase separation offer a confined space where protein-protein interactions (PPIs) facilitate distinct biochemical reactions. As their aberrant behavior is associated with disease, it is crucial to understand the molecular organization of PPIs within condensates. Using quantitative time-resolved crosslinking mass spectrometry (XL-MS) we directly and specifically monitor PPIs and protein dynamics inside condensates formed by the protein fused in sarcoma (FUS) and identify its folded RNA recognition motif (RRM) as a key player of aberrant molecular aging. We find that the chaperone HspB8, but not a disease-associated mutant, prevents FUS aging. In XL-MS and partitioning experiments we find that the disordered region of HspB8 directs its α-crystallin domain (αCD) into FUS droplets where HspB8 prevents aging via condensate-specific αCD–RRM interactions. We propose that chaperones like HspB8 prevent aberrant phase transitions by stabilizing aggregation prone folded domains inside condensates in times of cellular stress.
HostingRepositoryPRIDE
AnnounceDate2021-10-13
AnnouncementXMLSubmission_2021-10-12_23:15:20.791.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFlorian Stengel
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-08-25 09:25:39ID requested
12021-10-12 23:15:21announced
Publication List
Boczek EE, F, ü, rsch J, Niedermeier ML, Jawerth L, Jahnel M, Ruer-Gru, ß M, Kammer KM, Heid P, Mediani L, Wang J, Yan X, Pozniakovski A, Poser I, Mateju D, Hubatsch L, Carra S, Alberti S, Hyman AA, Stengel F, HspB8 prevents aberrant phase transitions of FUS by chaperoning its folded RNA-binding domain. Elife, 10():(2021) [pubmed]
Keyword List
submitter keyword: FUS, aging, chaperone, structural proteomics, time-resolved quantitative XL-MS, RRM, protein dynamics, molecular condensates
Contact List
Florian Stengel
contact affiliationUniversity of Konstanz;Biology
contact emailflorian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliationUniversität Konstanz
contact emailflorian.stengel@uni-konstanz.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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Repository Record List
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