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利用化学蛋白质组学解析蛋白质脂化的生物学和可成药性。

Deconvoluting the biology and druggability of protein lipidation using chemical proteomics.

机构信息

Department of Chemistry, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, W12 0BZ, UK.

Department of Chemistry, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, W12 0BZ, UK.

出版信息

Curr Opin Chem Biol. 2021 Feb;60:97-112. doi: 10.1016/j.cbpa.2020.10.002. Epub 2020 Nov 20.

DOI:10.1016/j.cbpa.2020.10.002
PMID:33221680
Abstract

Lipids are indispensable cellular building blocks, and their post-translational attachment to proteins makes them important regulators of many biological processes. Dysfunction of protein lipidation is also implicated in many pathological states, yet its systematic analysis presents significant challenges. Thanks to innovations in chemical proteomics, lipidation can now be readily studied by metabolic tagging using functionalized lipid analogs, enabling global profiling of lipidated substrates using mass spectrometry. This has spearheaded the first deconvolution of their full scope in a range of contexts, from cells to pathogens and multicellular organisms. Protein N-myristoylation, S-acylation, and S-prenylation are the most well-studied lipid post-translational modifications because of their extensive contribution to the regulation of diverse cellular processes. In this review, we focus on recent advances in the study of these post-translational modifications, with an emphasis on how novel mass spectrometry methods have elucidated their roles in fundamental biological processes.

摘要

脂质是细胞不可缺少的组成部分,其翻译后的蛋白质结合使其成为许多生物过程的重要调节剂。蛋白质脂质化功能障碍也与许多病理状态有关,但对其进行系统分析具有很大的挑战性。感谢化学蛋白质组学的创新,现在可以使用功能化脂质类似物通过代谢标记轻松研究脂质化,从而使用质谱法对脂质化底物进行全面分析。这首先在从细胞到病原体和多细胞生物的一系列环境中对其进行了全面剖析。蛋白质 N-豆蔻酰化、S-酰化和 S-异戊烯基化是研究最多的脂质翻译后修饰,因为它们对调节多种细胞过程有广泛的贡献。在这篇综述中,我们重点介绍了这些翻译后修饰研究的最新进展,重点介绍了新型质谱方法如何阐明它们在基本生物过程中的作用。

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