Non-enzymatic protein modifications at the interface of metabolism and immunity

IF 9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology Pub Date : 2026-10-15 Epub Date: 2026-10-06 DOI:10.1016/j.chembiol.2026.09.005

Nicole S. Walker, James J. Galligan, Yael David, Anna Knörlein

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Abstract

Immune cells are highly metabolically active throughout their life cycle, leading to elevated levels of a variety of reactive metabolites including reactive oxygen species, sugars, and lipid peroxidation products. These molecules covalently modify proteins, resulting in post-translational non-enzymatic covalent modifications (NECMs). Similar to their enzymatic counterparts, NECMs impact proteins’ structure, stability, localization, function, and interactome, thereby shaping cellular behavior, providing an additional layer of regulation to leukocyte function. With increasing evidence linking metabolic dysregulation to dysfunction of immune cells, it is becoming critical to understand the role NECMs play in regulating immune cell fate. This review highlights recent advances in our understanding of NECMs in immune cell function, including their roles in inflammation and immune responses. We further discuss emerging chemical biology technologies to detect, interrogate, and manipulate these modifications while outlining key challenges that will shape future studies of non-enzymatic protein modifications in immune regulation.

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代谢和免疫界面的非酶蛋白修饰

免疫细胞在其整个生命周期中具有高度的代谢活性，导致各种活性代谢物水平升高，包括活性氧、糖和脂质过氧化产物。这些分子共价修饰蛋白质，导致翻译后非酶共价修饰（necm）。与它们的酶对应物类似，necm影响蛋白质的结构、稳定性、定位、功能和相互作用，从而塑造细胞行为，为白细胞功能提供额外的调节层。随着越来越多的证据将代谢失调与免疫细胞功能障碍联系起来，了解necm在调节免疫细胞命运中的作用变得至关重要。这篇综述强调了我们对necm在免疫细胞功能中的理解的最新进展，包括它们在炎症和免疫反应中的作用。我们进一步讨论了新兴的化学生物学技术，以检测、询问和操纵这些修饰，同时概述了将影响免疫调节中非酶蛋白修饰未来研究的关键挑战。免疫细胞在其整个生命周期中具有高度的代谢活性，导致各种活性代谢物水平升高，包括活性氧、糖和脂质过氧化产物。这些分子共价修饰蛋白质，导致翻译后非酶共价修饰（necm）。与它们的酶对应物类似，necm影响蛋白质的结构、稳定性、定位、功能和相互作用，从而塑造细胞行为，为白细胞功能提供额外的调节层。随着越来越多的证据将代谢失调与免疫细胞功能障碍联系起来，了解necm在调节免疫细胞命运中的作用变得至关重要。这篇综述强调了我们对necm在免疫细胞功能中的理解的最新进展，包括它们在炎症和免疫反应中的作用。我们进一步讨论了新兴的化学生物学技术，以检测、询问和操纵这些修饰，同时概述了将影响免疫调节中非酶蛋白修饰未来研究的关键挑战。下载：下载高分辨率图片（141KB）下载：下载全尺寸图片

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来源期刊

Cell Chemical Biology Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

14.70

自引率

2.30%

发文量

143

期刊介绍： Cell Chemical Biology, a Cell Press journal established in 1994 as Chemistry & Biology, focuses on publishing crucial advances in chemical biology research with broad appeal to our diverse community, spanning basic scientists to clinicians. Pioneering investigations at the chemistry-biology interface, the journal fosters collaboration between these disciplines. We encourage submissions providing significant conceptual advancements of broad interest across chemical, biological, clinical, and related fields. Particularly sought are articles utilizing chemical tools to perturb, visualize, and measure biological systems, offering unique insights into molecular mechanisms, disease biology, and therapeutics.