光诱导靶向技术实现了对内源性凝聚物的蛋白质组学研究

IF 5.7 1区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Chemical Theory and Computation Pub Date : 2024-10-18 DOI:10.1016/j.cell.2024.09.040

Choongman Lee, Andrea Quintana, Ida Suppanz, Alejandro Gomez-Auli, Gerhard Mittler, Ibrahim I. Cissé

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引用次数: 0

摘要

具有瞬时成分的内源凝集物很难用质谱法和其他蛋白质组学分析等普通生物检测方法进行研究。在这里，我们报告了一种在活细胞中光诱导靶向内源凝聚物（LiTEC）的方法。LiTEC 将识别靶向内源凝集物的分子代码与光遗传学相结合，以蓝光依赖的方式将任意货物（如蛋白质组学中常用的酶）可控、可逆地分配到凝集物中。我们通过将 LiTEC 与基于邻近性的生物素化（BioID）相结合，证明了这一概念，并发现了小鼠胚胎干细胞中转录凝聚物的假定成分。我们的方法为内源凝聚物的全基因组功能研究开辟了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Light-induced targeting enables proteomics on endogenous condensates

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Light-induced targeting enables proteomics on endogenous condensates

Endogenous condensates with transient constituents are notoriously difficult to study with common biological assays like mass spectrometry and other proteomics profiling. Here, we report a method for light-induced targeting of endogenous condensates (LiTEC) in living cells. LiTEC combines the identification of molecular zip codes that target the endogenous condensates with optogenetics to enable controlled and reversible partitioning of an arbitrary cargo, such as enzymes commonly used in proteomics, into the condensate in a blue light-dependent manner. We demonstrate a proof of concept by combining LiTEC with proximity-based biotinylation (BioID) and uncover putative components of transcriptional condensates in mouse embryonic stem cells. Our approach opens the road to genome-wide functional studies of endogenous condensates.

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来源期刊

Journal of Chemical Theory and Computation 化学-物理：原子、分子和化学物理

CiteScore

9.90

自引率

16.40%

发文量

568

审稿时长

1 months

期刊介绍： The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.