{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jiang Y"],"funding":["NIGMS NIH HHS"],"pagination":["eads7379"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11908495"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(11)"],"pubmed_abstract":["Stretched-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 extensi"],"journal":["Science advances"],"pubmed_title":["Protein misfolding involving entanglements providesa structural explanation for the origin of stretched-exponential refolding kinetics."],"pmcid":["PMC11908495"],"funding_grant_id":["R35 GM124818"],"pubmed_authors":["Jiang Y","Xia Y","Sharma P","Sitarik I","Fried SD","O'Brien EP","Song H"],"additional_accession":[]},"is_claimable":false,"name":"Protein misfolding involving entanglements providesa structural explanation for the origin of stretched-exponential refolding kinetics.","description":"Stretched-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 extensi","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-01T05:45:19.028Z","creation":"2025-04-04T14:48:13.631Z"},"accession":"S-EPMC11908495","cross_references":{"pubmed":["40085700"],"doi":["10.1126/sciadv.ads7379"]}}