以肽为中心的局部稳定性分析使蛋白质组级鉴定蛋白质靶标和不同配体的结合区域成为可能。

IF 36.1 1区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Nature Methods Pub Date : 2024-12-10 DOI:10.1038/s41592-024-02553-7

Kejia Li, Shijie Chen, Keyun Wang, Yan Wang, Lianji Xue, Yuying Ye, Zheng Fang, Jiawen Lyu, Haiyang Zhu, Yanan Li, Ting Yu, Feng Yang, Xiaolei Zhang, Siqi Guo, Chengfei Ruan, Jiahua Zhou, Qi Wang, Mingming Dong, Cheng Luo, Mingliang Ye

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引用次数: 0

摘要

通过使用有限的蛋白水解策略，使用大量胰蛋白酶直接从天然蛋白产生肽，我们发现配体诱导的蛋白质局部稳定性变化可以在蛋白质组范围内灵敏地检测到。这使我们能够开发以肽为中心的局部稳定性测定，这是一种无修饰的方法，在蛋白质组范围内的目标鉴定和结合区测定中实现了前所未有的灵敏度。我们通过研究各种生物背景下的相互作用，展示了肽中心局部稳定性测定的广泛应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands

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A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands

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.

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来源期刊

Nature Methods 生物-生化研究方法

CiteScore

58.70

自引率

1.70%

发文量

326

审稿时长

1 months

期刊介绍： Nature Methods is a monthly journal that focuses on publishing innovative methods and substantial enhancements to fundamental life sciences research techniques. Geared towards a diverse, interdisciplinary readership of researchers in academia and industry engaged in laboratory work, the journal offers new tools for research and emphasizes the immediate practical significance of the featured work. It publishes primary research papers and reviews recent technical and methodological advancements, with a particular interest in primary methods papers relevant to the biological and biomedical sciences. This includes methods rooted in chemistry with practical applications for studying biological problems.