Xu Xingye, Hu Xiangqi, Dong Jie, Xue Ying, Liu Tao, Jin Qi
NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Genet. 2022 Mar 10;13:832668. doi: 10.3389/fgene.2022.832668. eCollection 2022.
Lysine crotonylation is a newly discovered post-translational modification (PTM) with key roles in various important regulatory pathways. Despite its functional significance, there is limited knowledge about crotonylation in fungi. is the most common fungal pathogen in human infection and is considered a model organism of dermatophytes and human pathogenic filamentous fungi. In this study, we obtained a proteome-wide crotonylation profile of , leading to the identification of 14,019 crotonylated sites on 3144 proteins. The crotonylated proteins were significantly involved in translation and in various metabolic and biosynthetic processes. Some proteins related to fungal pathogenicity were also found to be targets of crotonylation. In addition, extensive crotonylation was found on histones, suggesting a role in epigenetic regulation. Furthermore, about half of the crotonylated proteins were specific to either the conidial or the mycelial stage, and functional enrichment analysis showed some differences between the two stages. The results suggest that the difference in crotonylation between the two stages is not due to differences in protein abundance. Crosstalk of crotonylation with acetylation, propionylation, and succinylation suggests distinct regulatory roles. This study is the first crotonylation analysis in dermatophytes and human pathogenic filamentous fungi. These results represent a solid foundation for further research on PTM regulatory mechanisms in fungi and should facilitate improved antifungal strategies against these medical important species.
赖氨酸巴豆酰化是一种新发现的翻译后修饰（PTM），在各种重要的调控途径中发挥关键作用。尽管其具有功能重要性，但关于真菌中巴豆酰化的知识却很有限。 是人类感染中最常见的真菌病原体，被认为是皮肤癣菌和人类致病丝状真菌的模式生物。在本研究中，我们获得了该菌全蛋白质组范围的巴豆酰化图谱，鉴定出3144个蛋白质上的14019个巴豆酰化位点。巴豆酰化的蛋白质显著参与翻译以及各种代谢和生物合成过程。还发现一些与真菌致病性相关的蛋白质是巴豆酰化的靶点。此外，在组蛋白上发现了广泛的巴豆酰化，表明其在表观遗传调控中发挥作用。此外，约一半的巴豆酰化蛋白质在分生孢子期或菌丝期具有特异性，功能富集分析显示两个阶段之间存在一些差异。结果表明，两个阶段之间巴豆酰化的差异并非由于蛋白质丰度的差异。巴豆酰化与乙酰化、丙酰化和琥珀酰化的相互作用表明其具有不同的调控作用。本研究是首次对皮肤癣菌和人类致病丝状真菌进行巴豆酰化分析。这些结果为进一步研究真菌中PTM调控机制奠定了坚实基础，并应有助于改进针对这些医学重要真菌的抗真菌策略。
