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PXD053579

PXD053579 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProtein misfolding involving entanglements provides a structural explanation for the origin of stretched-exponential refolding kinetics
DescriptionStretched-exponential protein refolding kinetics, first observed decades ago, were attributed to a nonnative ensemble of structures with parallel, non-interconverting folding pathways. However, the structural origin of the large energy barriers preventing interconversion between these folding pathways is unknown. Here, we combine simulations with limited proteolysis (LiP) and cross-linking (XL) mass spectrometry (MS) to study the protein phosphoglycerate kinase (PGK). Simulations recapitulate its stretched-exponential folding kinetics and reveal that misfolded states involving changes of entanglement underlie this behavior: either formation of a nonnative, noncovalent lasso entanglement or failure to form a native entanglement. These misfolded states act as kinetic traps, requiring extensive unfolding to escape, which results in a distribution of free energy barriers and pathway partitioning. Using LiP-MS and XL-MS, we propose heterogeneous structural ensembles consistent with these data that represent the potential long-lived misfolded states PGK populates. This structural and energetic heterogeneity creates a hierarchy of refolding timescales, explaining stretched-exponential kinetics.
HostingRepositoryPRIDE
AnnounceDate2025-03-18
AnnouncementXMLSubmission_2025-03-17_18:35:09.033.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYingzi Xia
SpeciesList scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-02 14:59:43ID requested
12025-03-17 18:35:09announced
Publication List
Jiang Y, Xia Y, Sitarik I, Sharma P, Song H, Fried SD, O'Brien EP, Protein misfolding involving entanglements providesa structural explanation for the origin of stretched-exponential refolding kinetics. Sci Adv, 11(11):eads7379(2025) [pubmed]
10.1126/sciadv.ads7379;
Keyword List
submitter keyword: limited proteolisys mass spectrometry, stretched-exponential kinetics,refolding
Contact List
Stephen Fried
contact affiliationAssistant Professor, Department of Chemistry Assistant Professor, Department of Biology (by courtesy) Assistant Professor, Thomas C. Jenkins Department of Biophysics (by courtesy) Preceptor, Chemistry-Biology Interface (CBI) Program
contact emailsdfried@jhu.edu
lab head
Yingzi Xia
contact affiliationJohns Hopkins University
contact emailyxia39@jhu.edu
dataset submitter
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Dataset FTP location
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