精氨酸激酶 McsB 的复合结构和 McsA 激活机制

IF 12.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kai Lu, Bingnan Luo, Xuan Tao, Yongbo Luo, Mingjun Ao, Bin Zheng, Xiang Xu, Xiaoyan Ma, Jingling Niu, Huinan Li, Yanxuan Xie, Zhennan Zhao, Peng Zheng, Guanbo Wang, Song Gao, Chao Wang, Wei Xia, Zhaoming Su, Zong-Wan Mao
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引用次数: 0

摘要

蛋白质磷酸化是调节各种细胞过程的关键性翻译后修饰。在革兰氏阳性细菌中,蛋白质精氨酸激酶 McsB 及其激活剂 McsA 在应激过程中标记错误折叠和受损蛋白质方面起着关键作用。然而,McsA 对 McsB 的激活机制仍然难以捉摸。在这里,我们以 3.41 Å 的分辨率报告了四聚体 McsA-McsB 复合物的冷冻电镜结构。生化分析表明,同源四聚体组装对 McsB 的激酶活性至关重要。McsA 保守的 C 端锌指与 McsB 的一个延长环相互作用,使一个关键的催化半胱氨酸残基定向最佳。此外,McsA 的结合会降低 CtsR 对 McsB 的亲和力,增强 McsB 的激酶活性,加快 CtsR 磷酸化的周转率。此外,McsA 的结合还能提高 McsB 的热稳定性,确保其在热应力下的活性。这些发现阐明了McsB在应激反应中的结构基础和激活机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Complex structure and activation mechanism of arginine kinase McsB by McsA

Complex structure and activation mechanism of arginine kinase McsB by McsA

Protein phosphorylation is a pivotal post-translational modification modulating various cellular processes. In Gram-positive bacteria, the protein arginine kinase McsB, along with its activator McsA, has a key role in labeling misfolded and damaged proteins during stress. However, the activation mechanism of McsB by McsA remains elusive. Here we report the cryo-electron microscopy structure of a tetrameric McsA–McsB complex at 3.41 Å resolution. Biochemical analysis indicates that the homotetrameric assembly is essential for McsB’s kinase activity. The conserved C-terminal zinc finger of McsA interacts with an extended loop in McsB, optimally orienting a critical catalytic cysteine residue. In addition, McsA binding decreases the CtsR’s affinity for McsB, enhancing McsB’s kinase activity and accelerating the turnover rate of CtsR phosphorylation. Furthermore, McsA binding also increases McsB’s thermostability, ensuring its activity under heat stress. These findings elucidate the structural basis and activation mechanism of McsB in stress response.

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来源期刊
Nature chemical biology
Nature chemical biology 生物-生化与分子生物学
CiteScore
23.90
自引率
1.40%
发文量
238
审稿时长
12 months
期刊介绍: Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.
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