⮝ Full datasets listing

PXD049463

PXD049463 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHDX-MS finds that partial unfolding with sequential domain activation controls condensation of a cellular stress marker
DescriptionPoly(A)-binding protein (Pab1), a canonical stress granule marker, condenses upon heat shock or starvation, promoting adaptation, The molecular basis of condensation has remained elusive due to a dearth of techniques to probe structure directly in condensates. Here we apply hydrogendeuterium exchange/mass spectrometry (HDX-MS) to investigate the molecular mechanism of Pab1’s condensation. We find that Pab1’s four RNA recognition motifs (RRMs) undergo different levels of partial unfolding upon condensation, and the changes are similar for thermal and pH stresses. Although structural heterogeneity is observed, the ability of MS to describe individual subpopulations allows us to identify which regions become partially unfolded and contribute to the condensate’s interaction network. Our data yield a clear molecular picture of Pab1’s stresstriggered condensation, which we term sequential activation, wherein each RRM becomes activated at a temperature where it partially unfolds and associates with other likewise activated RRMs to form the condensate. This model thus implies that sequential activation is dictated by the underlying free energy surface, an effect we refer to as thermodynamic specificity. Our study represents a methodological advance for elucidating the interactions that drive biomolecular condensation that we anticipate will be widely applicable. Furthermore, our findings demonstrate how condensation can use thermodynamic specificity to perform an acute response to multiple stresses, a potentially general mechanism for stress-responsive proteins.
HostingRepositoryPRIDE
AnnounceDate2024-03-22
AnnouncementXMLSubmission_2024-03-21_18:30:23.931.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRuofan Chen
SpeciesList scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-18 05:13:56ID requested
12024-03-21 18:30:24announced
Publication List
10.1073/PNAS.2321606121;
Keyword List
submitter keyword: hydrogen exchange, cellular stress response, mass spectrometry, Pab1,Liquid-liquid phase separation
Contact List
Tobin R.
contact affiliationDepartment of Biochemistry and Molecular Biology, University of Chicago
contact emailtrsosnic@uchicago.edu
lab head
Ruofan Chen
contact affiliationUniversity of Chicago
contact emailruofanchen0@gmail.com
dataset submitter
Full Dataset Link List
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/2024/03/PXD049463
PRIDE project URI
Repository Record List
[ + ]