Protein arginine methylation rewires molecular interactions

IF 9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology Pub Date : 2026-10-15 DOI:10.1016/j.chembiol.2026.09.011

Joseph D. DeAngelo, Aliza M. Silverstein, David Shechter

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Abstract

Protein arginine methyltransferases (PRMT1–9) catalyze monomethylation and dimethylation of arginine residues in RNA- and DNA-associated proteins. Protein arginine methylation can weaken or strengthen nucleic acid binding, recruit or exclude protein partners, and promote or suppress higher-order assembly, making its molecular consequences highly context dependent. Methylation preserves the cationic character of the guanidinium group, while altering hydrogen-bond donor topology, steric accessibility, and interaction geometry. These effects are particularly consequential in intrinsically disordered regions (IDRs), where arginine-rich motifs mediate multivalent protein-protein and protein-nucleic acid interactions. Here, we propose an interaction-equilibrium framework in which arginine methylation redistributes binding capacity among the competing protein, nucleic acid, and assembly states. This framework integrates reader-dependent and reader-independent effects of methylarginine and provides a chemical basis for understanding how a charge-preserving modification can reweight molecular interactions across diverse cellular contexts.

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蛋白质精氨酸甲基化改变了分子间的相互作用

蛋白精氨酸甲基转移酶（PRMT1-9）催化RNA和dna相关蛋白中精氨酸残基的单甲基化和二甲基化。蛋白精氨酸甲基化可以削弱或加强核酸结合，招募或排除蛋白伴侣，促进或抑制高阶组装，使其分子后果高度依赖于环境。甲基化保留了胍基的阳离子特征，同时改变了氢键供体拓扑结构、立体可及性和相互作用的几何形状。这些影响在内在无序区（IDRs）尤其重要，在那里富含精氨酸的基序介导多价蛋白-蛋白和蛋白质-核酸相互作用。在这里，我们提出了一个相互作用平衡框架，其中精氨酸甲基化重新分配了相互竞争的蛋白质、核酸和组装状态之间的结合能力。该框架整合了甲基精氨酸的读者依赖效应和读者独立效应，并为理解电荷保持修饰如何在不同细胞环境下重新调整分子相互作用提供了化学基础。

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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.