一种以肽为中心的局部稳定性分析方法能够在蛋白质组规模上鉴定各种配体的蛋白质靶点和结合区域。
A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands.
作者信息
Li Kejia, Chen Shijie, Wang Keyun, Wang Yan, Xue Lianji, Ye Yuying, Fang Zheng, Lyu Jiawen, Zhu Haiyang, Li Yanan, Yu Ting, Yang Feng, Zhang Xiaolei, Guo Siqi, Ruan Chengfei, Zhou Jiahua, Wang Qi, Dong Mingming, Luo Cheng, Ye Mingliang
机构信息
State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian, China.
University of Chinese Academy of Sciences, Beijing, China.
出版信息
Nat Methods. 2025 Feb;22(2):278-282. doi: 10.1038/s41592-024-02553-7. Epub 2024 Dec 10.
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.
通过使用一种有限蛋白酶解策略，即使用大量胰蛋白酶直接从天然蛋白质中生成肽段，我们发现配体诱导的蛋白质局部稳定性变化可以在全蛋白质组范围内被灵敏地检测到。这使我们能够开发以肽为中心的局部稳定性分析方法，这是一种无需修饰的方法，在全蛋白质组范围内的靶点识别和结合区域确定方面实现了前所未有的灵敏度。我们通过研究各种生物学背景下的相互作用，展示了以肽为中心的局部稳定性分析方法的广泛应用。
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