
Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: March 11, 2024
ABSTRACT The FragPipe computational proteomics platform is gaining widespread popularity among the research community because of its fast processing speed and user-friendly graphical interface. Although produces well-formatted output tables that are ready for analysis, there still a need an easy-to-use downstream statistical analysis visualization tool. FragPipe-Analyst addresses this by providing R shiny web server to assist users in conducting analyses resulting quantitative data. It supports major quantification workflows including label-free quantification, tandem mass tags, data-independent acquisition. offers range useful functionalities, such as various missing value imputation options, data quality control, unsupervised clustering, differential expression (DE) using Limma, gene ontology pathway enrichment Enrichr. To support advanced customized visualizations, we also developed FragPipeAnalystR, package encompassing all functionalities extended site-specific post-translational modifications (PTMs). FragPipeAnalystR both open-source freely available.
Language: Английский
Citations
13Science Advances, Journal Year: 2025, Volume and Issue: 11(11)
Published: March 14, 2025
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 large energy barriers preventing interconversion between these pathways is unknown. Here, we combine simulations limited proteolysis (LiP) and cross-linking (XL) mass spectrometry (MS) study phosphoglycerate kinase (PGK). Simulations recapitulate its stretched-exponential kinetics reveal that misfolded states involving changes entanglement underlie this behavior: either formation nonnative, noncovalent lasso or failure form native entanglement. These act as kinetic traps, requiring extensive unfolding escape, which results in distribution free pathway partitioning. Using LiP-MS XL-MS, propose heterogeneous ensembles consistent data represent potential long-lived PGK populates. This energetic heterogeneity creates hierarchy timescales, explaining kinetics.
Language: Английский
Citations
0bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: July 29, 2024
Abstract Cellular desiccation - the loss of nearly all water from cell is a recurring stress in an increasing number ecosystems that can drive protein unfolding and aggregation. For cells to survive, at least some proteome must resume function upon rehydration. Which proteins tolerate desiccation, molecular determinants underlie this tolerance, are largely unknown. Here, we apply quantitative structural proteomic mass spectrometry show certain possess innate capacity rehydration following extreme loss. Structural analysis points surface chemistry as key determinant for which test by showing rational mutants convert sensitive into tolerant one. Desiccation tolerance also has strong overlap with cellular function, highly responsible production small molecule building blocks, intolerant involved energy-consuming processes such ribosome biogenesis. As result, rehydrated preferentially enriched metabolite producers depleted cell’s heaviest consumers. We propose functional bias enables kickstart their metabolism promote survival Teaser Proteins resist dryness tuning amino acids on surfaces.
Language: Английский
Citations
2PRX Life, Journal Year: 2024, Volume and Issue: 2(3)
Published: Sept. 9, 2024
One of the planet's more understudied ecosystems is deep biosphere, where organisms can experience high hydrostatic pressures (30–110 MPa); yet, by current estimates, these subsurface and ocean zones host majority Earth's microbial animal life. The extent to which terrestrially relevant up 100 MPa deform most globular proteins—and kinds—has not been established. Here, we report invention an experimental apparatus that enables structural proteomic methods be carried out at for first time. method, called high-pressure limited proteolysis (Hi-P LiP), involves performing pulse on whole cell extracts brought pressure. resulting sites proteolytic susceptibility induced pressure are subsequently read sequencing peptide fragments with tandem liquid chromatography–mass spectrometry. method sensitively detects pressure-induced changes residue resolution proteomes, providing a broad view effect protein structure. When applied piezosensitive thermophilic bacterium, , find approximately 40% its soluble proteome structurally perturbed MPa. Proteins lower charge density resistant deformation, as expected; however, contrary expectations, proteins packing (i.e., voids) also deformation. Furthermore, has previously shown preferentially alter conformations around active sites. show this observed in Hi-P LiP, suggesting could provide generic unbiased modality detect binding scale. Hence, data sets kind prove useful training emerging artificial intelligence models predict cryptic greater accuracy. Published American Physical Society 2024
Language: Английский
Citations
2Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
0