A family of bacterial Josephin-like deubiquitinases with an irreversible cleavage mode

IF 14.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell Pub Date : 2025-03-03 DOI:10.1016/j.molcel.2025.02.002

Thomas Hermanns, Susanne Kolek, Matthias Uthoff, Richard A. de Heiden, Monique P.C. Mulder, Ulrich Baumann, Kay Hofmann

{"title":"A family of bacterial Josephin-like deubiquitinases with an irreversible cleavage mode","authors":"Thomas Hermanns, Susanne Kolek, Matthias Uthoff, Richard A. de Heiden, Monique P.C. Mulder, Ulrich Baumann, Kay Hofmann","doi":"10.1016/j.molcel.2025.02.002","DOIUrl":null,"url":null,"abstract":"Many intracellular bacteria secrete deubiquitinase (DUB) effectors into eukaryotic host cells to keep the bacterial surface or the enclosing vesicle membrane free of ubiquitin marks. This study describes a family of DUBs from several bacterial genera, including Simkania, Parachlamydia, Burkholderia, and Pigmentiphaga, which is structurally related to eukaryotic Josephin-type DUBs but contains members that catalyze a unique destructive substrate deubiquitination. These ubiquitin C-terminal clippases (UCCs) cleave ubiquitin before the C-terminal diGly motif, thereby truncating the modifier and leaving a remnant on the substrate. By comparing the crystal structures of substrate-bound clippases and a closely related conventional DUB, we identified the factors causing this shift and found them to be conserved in other clippases, including one highly specific for M1-linked ubiquitin chains. This enzyme class has great potential to serve as tools for studying the ubiquitin system, particularly aspects involving branched chains.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"66 1","pages":""},"PeriodicalIF":14.5000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.molcel.2025.02.002","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Many intracellular bacteria secrete deubiquitinase (DUB) effectors into eukaryotic host cells to keep the bacterial surface or the enclosing vesicle membrane free of ubiquitin marks. This study describes a family of DUBs from several bacterial genera, including Simkania, Parachlamydia, Burkholderia, and Pigmentiphaga, which is structurally related to eukaryotic Josephin-type DUBs but contains members that catalyze a unique destructive substrate deubiquitination. These ubiquitin C-terminal clippases (UCCs) cleave ubiquitin before the C-terminal diGly motif, thereby truncating the modifier and leaving a remnant on the substrate. By comparing the crystal structures of substrate-bound clippases and a closely related conventional DUB, we identified the factors causing this shift and found them to be conserved in other clippases, including one highly specific for M1-linked ubiquitin chains. This enzyme class has great potential to serve as tools for studying the ubiquitin system, particularly aspects involving branched chains.

Abstract Image

查看原文本刊更多论文

具有不可逆裂解模式的细菌约瑟芬样去泛素化酶家族

许多胞内细菌分泌去泛素酶（DUB）效应物进入真核宿主细胞，以保持细菌表面或包裹的囊泡膜无泛素标记。本研究描述了来自几个细菌属的DUBs家族，包括Simkania，副原体，Burkholderia和Pigmentiphaga，它在结构上与真核josephin型DUBs相关，但包含催化独特的破坏性底物去泛素化的成员。这些泛素c端剪切酶（UCCs）在泛素c端diGly基序之前剪切泛素，从而截断修饰子并在底物上留下残余物。通过比较底物结合的剪切酶和密切相关的传统DUB的晶体结构，我们确定了导致这种转变的因素，并发现它们在其他剪切酶中是保守的，包括一个对m1连接的泛素链高度特异性的剪切酶。这类酶具有很大的潜力，可以作为研究泛素系统的工具，特别是涉及支链的方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Cell 生物-生化与分子生物学

CiteScore

26.00

自引率

3.80%

发文量

389

审稿时长

1 months

期刊介绍： Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.