Laboratory of Oral Microbiology, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Proc Natl Acad Sci U S A. 2024 Oct 8;121(41):e2407820121. doi: 10.1073/pnas.2407820121. Epub 2024 Oct 2.
Protein acetylation is a common and reversible posttranslational modification tightly governed by protein acetyltransferases and deacetylases crucial for various biological processes in both eukaryotes and prokaryotes. Although recent studies have characterized many acetyltransferases in diverse bacterial species, only a few protein deacetylases have been identified in prokaryotes, perhaps in part due to their limited sequence homology. In this study, we identified YkuR, encoded by , as a unique protein deacetylase in . Through protein acetylome analysis, we demonstrated that the deletion of significantly upregulated protein acetylation levels, affecting key enzymes in translation processes and metabolic pathways, including starch and sucrose metabolism, glycolysis/gluconeogenesis, and biofilm formation. In particular, YkuR modulated extracellular polysaccharide synthesis and biofilm formation through the direct deacetylation of glucosyltransferases (Gtfs) in the presence of NAD. Intriguingly, YkuR can be acetylated in a nonenzymatic manner, which then negatively regulated its deacetylase activity, suggesting the presence of a self-regulatory mechanism. Moreover, in vivo studies further demonstrated that the deletion of attenuated the cariogenicity of in the rat caries model, substantiating its involvement in the pathogenesis of dental caries. Therefore, our study revealed a unique regulatory mechanism mediated by YkuR through protein deacetylation that regulates the physiology and pathogenicity of .
蛋白质乙酰化是一种常见且可逆的翻译后修饰，由蛋白质乙酰转移酶和去乙酰化酶严格调控，对真核生物和原核生物中的各种生物学过程都至关重要。尽管最近的研究已经在许多不同的细菌物种中鉴定了许多乙酰转移酶，但在原核生物中仅鉴定了少数几个蛋白质去乙酰化酶，这也许部分是由于它们的序列同源性有限。在这项研究中，我们鉴定出编码的 YkuR 是 中的一种独特的蛋白质去乙酰化酶。通过蛋白质乙酰化组分析，我们证明了的缺失显著上调了蛋白质乙酰化水平，影响了翻译过程和代谢途径中的关键酶，包括淀粉和蔗糖代谢、糖酵解/糖异生和生物膜形成。特别是，YkuR 通过 NAD 存在下的直向去乙酰化作用调节葡萄糖基转移酶（Gtfs），从而调节细胞外多糖合成和生物膜形成。有趣的是，YkuR 可以以非酶促方式被乙酰化，这随后负调控其去乙酰化酶活性，表明存在自我调控机制。此外，体内研究进一步表明，的缺失减弱了在大鼠龋齿模型中的致龋性，证实了其参与龋齿的发病机制。因此，我们的研究揭示了 YkuR 通过蛋白质去乙酰化介导的一种独特的调控机制，该机制调节 的生理学和致病性。
