PXD021115

PXD021115 is an original dataset announced via ProteomeXchange.

Title	HspB8 controls molecular aging of FUS condensates by domain-specific protein interactions Part 2
Description	Biomolecular 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.
HostingRepository	PRIDE
AnnounceDate	2021-10-13
AnnouncementXML	Submission_2021-10-12_23:15:20.791.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-25 09:25:39	ID requested
⏵ 1	2021-10-12 23:15:21	announced

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]

submitter keyword: FUS, aging, chaperone, structural proteomics, time-resolved quantitative XL-MS, RRM, protein dynamics, molecular condensates

Florian Stengel
contact affiliation	University of Konstanz;Biology
contact email	florian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
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/2021/10/PXD021115

PRIDE project URI

• PRIDE
  1. PXD021115
     1. Label: PRIDE project
     2. Name: HspB8 controls molecular aging of FUS condensates by domain-specific protein interactions Part 2