Nature chemical biology最新文献

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A single allosteric site merges activation, modulation and inhibition in TRPM5 一个单一的变构位点融合了TRPM5的激活、调节和抑制

IF 14.8 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2026-01-05 DOI: 10.1038/s41589-025-02097-7

Zheng Ruan, Junuk Lee, Yangyang Li, Ian J. Orozco, Juan Du, Wei Lü

引用次数: 0

The membrane transition strongly enhances biopolymer condensation through prewetting. 膜过渡通过预润湿强烈地促进了生物聚合物的缩聚。

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2026-01-02 DOI: 10.1038/s41589-025-02082-0

Yousef Bagheri, Mason N Rouches, Benjamin B Machta, Sarah L Veatch

Biopolymers that separate into condensed and dilute phases in solution also prewet membranes when one or more components couple to membrane lipids. Here we demonstrate that this prewetting transition becomes exquisitely sensitive to lipid composition when membranes have compositions near the boundary of liquid-ordered/liquid-disordered phase coexistence in both simulation and in reconstitution when polyelectrolytes are coupled to model membranes. In cells, we use an optogenetic tool to characterize prewetting at both the plasma membrane (PM) and the endoplasmic reticulum (ER) and find that prewetting is potentiated or inhibited by perturbations of membrane composition. Prewetting can also mediate membrane adhesion, with avidity dependent on membrane composition, as demonstrated in cells through the potentiation or inhibition of ER-PM contact sites. The strong correspondence of results in simulation, reconstitution and cells reveals a new role for membrane lipids in regulating the recruitment and assembly of soluble proteins.

当一种或多种组分与膜脂偶联时，在溶液中分离成浓缩相和稀相的生物聚合物也会预湿膜。在这里，我们证明，当膜在模拟和重构中具有接近液体有序/液体无序相共存边界的成分时，当聚电解质耦合到模型膜时，这种预润湿转变对脂质组成变得非常敏感。在细胞中，我们使用光遗传学工具来表征质膜（PM）和内质网（ER）的预润湿，并发现膜组成的扰动会增强或抑制预润湿。预湿也可以介导膜的粘附，其强度取决于膜的组成，正如在细胞中通过增强或抑制ER-PM接触位点所证明的那样。模拟、重构和细胞结果的强烈对应揭示了膜脂在调节可溶性蛋白募集和组装中的新作用。

引用次数: 0

Structural insights into type-I and type-II Lamassu antiphage systems. i型和ii型Lamassu抗噬菌体系统的结构见解。

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2026-01-02 DOI: 10.1038/s41589-025-02102-z

Ming Li, Xiaolong Zhao, Xingyu Zhao, Dong Li, Weijia Xiong, Zirui Gao, Ling Huang, Linfeng An, Yongxiang Gao, Shanshan Li, Yue Feng, Kaiming Zhang, Yi Zhang

Bacteria have developed a variety of immune systems to combat phage infections. The Lamassu system is a prokaryotic immune system with a core conserved structural maintenance of chromosomes (SMC) superfamily protein LmuB and diverse effectors named LmuA, whose mechanism remains unclear. Here we present a series of cryo-electron microscopy structures of the type-I Lamassu complex from Bacillus cellulasensis and the type-II Lamassu complex from Vibrio cholerae, both in apo and dsDNA-bound states, revealing an unexpected stoichiometry and topological architecture distinct from canonical SMC complexes. Combined structural and biochemical analyses show how the nuclease effector LmuA is sequestered in an inactive monomeric form within the Lamassu complex and, upon sensing foreign DNA ends, dissociates and assembles into an active tetramer capable of DNA cleavage. Our findings elucidate the mechanism by which Lamassu systems detect viral replication and implement antiphage defense, highlighting the roles of SMC proteins in prokaryotic immunity.

细菌已经发展出多种免疫系统来对抗噬菌体感染。Lamassu系统是一种原核免疫系统，其核心是染色体保守结构维持（SMC）超家族蛋白LmuB和多种名为LmuA的效应物，其机制尚不清楚。在这里，我们展示了一系列来自纤维素芽孢杆菌的i型Lamassu复合物和来自霍乱弧菌的ii型Lamassu复合物的低温电镜结构，无论是在载脂蛋白状态还是ddna结合状态，都揭示了与典型SMC复合物不同的意想不到的化学数量和拓扑结构。结合结构和生化分析表明，核酸酶效应物LmuA是如何以无活性单体形式隔离在Lamassu复合体内的，并且在感知外源DNA末端时，解离并组装成能够切割DNA的活性四聚体。我们的研究结果阐明了Lamassu系统检测病毒复制和实施噬菌体防御的机制，强调了SMC蛋白在原核免疫中的作用。

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引用次数: 0

PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates. PCMT1在CRBN底物上产生c端环亚胺基团。

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2025-12-29 DOI: 10.1038/s41589-025-02106-9

Zhenguang Zhao, Wenqing Xu, Ethan Yang Feng, Shiyun Cao, Alba Hermoso-López, Pablo Peña-Vega, Hannah C Lloyd, Abigail K D Porter, Manuel Guzmán, Ning Zheng, Christina M Woo

The E3 ligase substrate adapter cereblon (CRBN), the primary target of clinical agents thalidomide and lenalidomide, recognizes endogenous substrates bearing the C-terminal cyclic imide modification. Although C-terminal cyclic imides can form spontaneously, an enzyme that regulates their formation and thereby promotes a biological pathway connecting substrates to CRBN is unknown. Here we report that protein carboxymethyltransferase (PCMT1) promotes formation of C-terminal cyclic imides on C-terminal asparagine residues of CRBN substrates. PCMT1 and CRBN coregulate the levels of metabolic enzymes including glutamine synthetase and inorganic pyrophosphatase 1 in vitro, in cells and in vivo, and this regulation is associated with the proepileptic phenotype of CRBN knockout mouse models. The discovery of an enzyme that regulates CRBN substrates through the C-terminal cyclic imide reveals a previously unknown biological pathway that is perturbed by thalidomide derivatives and provides a biochemical basis for the connection between multiple biological processes and CRBN.

E3连接酶底物适配器小脑（CRBN）是临床药物沙利度胺和来那度胺的主要靶点，它识别带有c端环亚胺修饰的内源性底物。虽然c端环亚胺可以自发形成，但一种调节其形成从而促进底物与CRBN连接的生物途径的酶是未知的。在这里，我们报道了蛋白质羧甲基转移酶（PCMT1）促进CRBN底物c端天冬酰胺残基上c端环亚胺的形成。PCMT1和CRBN在体外、细胞内和体内共同调节谷氨酰胺合成酶和无机焦磷酸酶1等代谢酶的水平，这种调节与CRBN敲除小鼠模型的癫痫前表型有关。通过c端环亚胺调控CRBN底物的酶的发现，揭示了一个先前未知的被沙利度胺衍生物干扰的生物学途径，并为多个生物过程与CRBN之间的联系提供了生化基础。

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引用次数: 0

Writing the CRBN degron. 写CRBN学位。

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2025-12-29 DOI: 10.1038/s41589-025-02112-x

Marcus D Hartmann

引用次数: 0

Spatial barcoding reveals reaction radii and contact-dependent mechanism of proximity labeling 空间条形码揭示了邻近标记的反应半径和依赖于接触的机制

IF 14.8 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2025-12-24 DOI: 10.1038/s41589-025-02086-w

Zhe Yang, Yu Zhang, Yuxin Fang, Yuan Zhang, Jiasheng Du, Xiaowen Shen, Kecheng Zhang, Peng Zou, Zhixing Chen

Proximity labeling techniques such as TurboID and APEX2 have become pivotal tools for studying protein interactions. However, the spatial patterns of labeling methods within the submicrometer range remain poorly understood. Here we used DNA nanostructure platforms to precisely measure the labeling radii of TurboID and APEX2 through in vitro assays. Our DNA nanoruler design enables the deployment of oligonucleotide-barcoded labeling targets with nanometer precision near the enzymes. By quantifying labeling yields using qPCR and mapping them against target distances, we uncovered surprising insights into the labeling mechanisms. Contrary to the prevailing diffusive labeling model, our results demonstrate that TurboID primarily operates through contact-dependent labeling. Similarly, APEX2 shows high labeling efficiency within its direct contact range. In parallel, it exhibits low-level diffusive labeling toward more distant phenols. These findings reframe our understanding in the mechanism of proximity labeling enzymes while highlighting the potential of DNA nanotechnology in spatially profiling reactive species.

TurboID和APEX2等邻近标记技术已成为研究蛋白质相互作用的关键工具。然而，在亚微米范围内的标记方法的空间模式仍然知之甚少。本研究利用DNA纳米结构平台，通过体外实验精确测量TurboID和APEX2的标记半径。我们的DNA纳米控制器设计使寡核苷酸条形码标记靶标的部署具有纳米精度的酶附近。通过使用qPCR定量标记产量并将其映射到目标距离，我们发现了对标记机制的惊人见解。与流行的扩散标记模型相反，我们的结果表明，TurboID主要通过依赖于接触的标记来操作。同样，APEX2在其直接接触范围内显示出较高的标记效率。同时，它表现出对更远的酚的低水平扩散标记。这些发现重新构建了我们对接近标记酶机制的理解，同时强调了DNA纳米技术在空间分析反应性物种方面的潜力。

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引用次数: 0

Whale’s secret to long life 鲸鱼长寿的秘诀

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2025-12-22 DOI: 10.1038/s41589-025-02118-5

Majda Bratovič

引用次数: 0

Dueling multimers 决斗多聚体

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2025-12-22 DOI: 10.1038/s41589-025-02116-7

Grant Miura

引用次数: 0

Helping sperm keep the beat 帮助精子保持活力

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2025-12-22 DOI: 10.1038/s41589-025-02119-4

Benjamin McIlwain

引用次数: 0

Clocking in for DNA repair 为DNA修复打卡

IF 13.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology

Pub Date : 2025-12-22 DOI: 10.1038/s41589-025-02120-x

Gene Chong

引用次数: 0

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