PXD021114

PXD021114 is an original dataset announced via ProteomeXchange.

Title	HspB8 controls hardening and molecular aging of FUS condensates by domain-specific protein interactions Part 1
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 increasingly associated with disease, it is crucial to understand the molecular organization of PPIs within condensates. Using quantitative and time-resolved crosslinkingmass spectrometry we directly and specifically monitor PPIs and protein dynamics of fused in sarcoma (FUS) condensates and identify its RNA recognition motif (RRM) as a key player of condensate-specific PPIs and aging. We find that the chaperone HspB8, but not a disease-associated mutant, prevents FUS aging. The disordered region of HspB8 directs its α-crystallin domain (αCD) into FUS condensates. Here, RRM unfolding drives aggregation but binding of HspB8 via a droplet-specific αCD – RRM interface significantly delays the onset of aging. We propose that chaperones such as HspB8 prevent aberrant phase transitions by stabilizing aggregation prone RNA binding domains in times of cellular stress.
HostingRepository	PRIDE
AnnounceDate	2021-10-12
AnnouncementXML	Submission_2021-10-12_22:58:37.870.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 09:25:34	ID requested
1	2021-10-12 07:20:24	announced
⏵ 2	2021-10-12 22:58:38	announced	2021-10-13: Updated publication reference for PubMed record(s): 34487489.

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: Phase separation, qXL-MS, FUS, HspB8, Hsp27, molecular aging

FLorian Stengel
contact affiliation	University of Konstanz; Biology departement
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/PXD021114

PRIDE project URI

• PRIDE
  1. PXD021114
     1. Label: PRIDE project
     2. Name: HspB8 controls hardening and molecular aging of FUS condensates by domain-specific protein interactions Part 1