Yuying Ye

Dec 10, 2024 | nature.com | Kejia Li |Shijie Chen |Keyun Wang |Yan Wang |Yuying Ye |Zheng Fang | +14 more

By using a limited-proteolysis strategy that employs a large amount of trypsin to generate peptides directly from native proteins, we found that ligand-induced protein local stability shifts can be sensitively detected on a proteome-wide scale. This enabled us to develop the peptide-centric local stability assay, a modification-free approach that achieves unprecedented sensitivity in proteome-wide target identification and binding-region determination. We demonstrate the broad applications of the peptide-centric local stability assay by investigating interactions across various biological contexts. The peptide-centric local stability assay (PELSA) can be used to determine ligand-binding targets and binding regions on a proteome-wide scale with high sensitivity.