High-ratiO partiaL proteolysiS with carriER proteome (HOLSER) Enables Global Structure Profiling and Site-resolved Elucidation of Ligand-Protein Interactions
Zhang, X.; Sokolova, B.; Meng, Z.; Gharibi, H.; Gaetani, M.; Zubarev, R.
Show abstract
Understanding how cellular proteins interact with their environment, including endogenous and exogeneous molecules, is critical for elucidating mechanisms of cellular regulation and drug action. Partial proteolysis-based techniques offer peptide-level resolution of ligand-induced conformational changes but are limited by modest proteome coverage and depth, as well as sensitivity to the experimental conditions. To overcome these limitations, we developed higH ratiO partiaL proteolysiS with carriER proteome (HOLSER), an efficient workflow that features extended digestion time for reduced peptide yield variability as well as tandem mass tag multiplexing that includes full digests for enhanced proteome depth and sequence coverage as well as higher precision of peptide abundance measurements. We demonstrate HOLSER capabilities of probing structural changes on the scale of specific binding sites for kinase target mapping, individual protein domains for structural mapping of the FKBP-mTOR complex in response to rapamycin as well as global proteome structure profiling.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Automated Enrichment of Phosphotyrosine Peptides for High-Throughput Proteomics 97%
- Increasing the Throughput and Reproducibility of Activity-Based Proteome Profiling Studies with Hyperplexing and Intelligent Data Acquisition 97%
- Inserting Pre-Analytical Chromatographic Priming Runs Significantly Improves Targeted Pathway Proteomics With Sample Multiplexing 97%
Similar papers in this journal
- System-wide profiling by proteome integral solubility alteration assay of drug residence times for target characterization 96%
- Top-down Proteomics for the Characterization and Quantification of Calreticulin Arginylation 96%
- Comparative assessment of quantification methods for tumor tissue phosphoproteomics 96%
Similar papers in this journal
Similar papers in this journal
- Photoredox-catalyzed decarboxylative C-terminal differentiation for bulk and single molecule proteomics 96%
- Novel substrate prediction for the TAM family of RTKs using phosphoproteomics and structure-based modeling 95%
- Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.