泛素特异性蛋白酶7的c端尾部促进泛素释放并确保有效的催化转换。

IF 4.5 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Biology Pub Date : 2025-06-16 DOI:10.1016/j.jmb.2025.169298

Emilie J. Korchak, Dane H. Geddes-Buehre, Irina Bezsonova

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引用次数: 0

摘要

USP7是参与人类发育的关键泛素特异性蛋白酶。它的活性是由催化结构域和非结构化c端尾部之间的分子内相互作用调节的。通过15N TROSY和13C甲基HMQC NMR，我们发现只有当USP7的催化结构域装载泛素时，c端肽才能与USP7的催化结构域结合。这种结合触发催化结构域的构象变化，促进泛素释放并确保有效的催化周转。这些发现为USP7激活提供了新的见解，可以为针对USP7治疗癌症和神经发育障碍提供治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The C-terminal Tail of Ubiquitin-Specific Protease 7 Facilitates Ubiquitin Release and Ensures Efficient Catalytic Turnover

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The C-terminal Tail of Ubiquitin-Specific Protease 7 Facilitates Ubiquitin Release and Ensures Efficient Catalytic Turnover

USP7 is a key ubiquitin-specific protease involved in human development. Its activity is regulated by an intramolecular interaction between the catalytic domain and the unstructured C-terminal tail. Using ¹⁵N TROSY and ¹³C methyl HMQC NMR spectroscopy, we show that the C-terminal peptide binds to USP7′s catalytic domain only when the domain is loaded with ubiquitin. This binding triggers conformational changes in the catalytic domain, facilitating ubiquitin release and ensuring efficient catalytic turnover. These findings provide new insights into USP7 activation, which could inform therapeutic strategies for targeting USP7 in cancer and neurodevelopmental disorders.

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来源期刊

Journal of Molecular Biology 生物-生化与分子生物学

CiteScore

11.30

自引率

1.80%

发文量

412

审稿时长

28 days

期刊介绍： Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions. Research areas include but are not limited to: Biomolecular interactions, signaling networks, systems biology; Cell cycle, cell growth, cell differentiation; Cell death, autophagy; Cell signaling and regulation; Chemical biology; Computational biology, in combination with experimental studies; DNA replication, repair, and recombination; Development, regenerative biology, mechanistic and functional studies of stem cells; Epigenetics, chromatin structure and function; Gene expression; Membrane processes, cell surface proteins and cell-cell interactions; Methodological advances, both experimental and theoretical, including databases; Microbiology, virology, and interactions with the host or environment; Microbiota mechanistic and functional studies; Nuclear organization; Post-translational modifications, proteomics; Processing and function of biologically important macromolecules and complexes; Molecular basis of disease; RNA processing, structure and functions of non-coding RNAs, transcription; Sorting, spatiotemporal organization, trafficking; Structural biology; Synthetic biology; Translation, protein folding, chaperones, protein degradation and quality control.