DataSheet1_Proteome-Wide Identification and Functional Analysis of Lysine Crotonylation in Trichophyton rubrum Conidial and Mycelial Stages.PDF

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. Trichophyton rubrum 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 T. rubrum, 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.

赖氨酸肉桂酰化作为一种新近发现的翻译后修饰（PTM），在众多重要的调控途径中扮演着核心角色。尽管其在功能上具有显著意义，但对于真菌中的肉桂酰化研究却知之甚少。毛癣菌（Trichophyton rubrum）是人类感染中最常见的真菌病原体，被视为皮肤癣菌和人类致病性丝状真菌的模式生物。在本研究中，我们获得了毛癣菌的全蛋白质组肉桂酰化谱，从而鉴定出3144种蛋白上的14019个肉桂酰化位点。肉桂酰化蛋白在翻译以及多种代谢和生物合成过程中发挥了显著作用。一些与真菌致病性相关的蛋白亦被发现是肉桂酰化的靶点。此外，组蛋白上的广泛肉桂酰化提示其在表观遗传调控中可能发挥作用。进一步地，约一半的肉桂酰化蛋白仅特异性地存在于分生孢子阶段或菌丝阶段，功能富集分析显示这两个阶段存在某些差异。结果表明，两个阶段肉桂酰化差异并非由蛋白质丰度差异所致。肉桂酰化与乙酰化、丙酰化和琥珀酰化之间的串扰表明其具有独特的调控作用。本研究是首次在皮肤癣菌和人类致病性丝状真菌中进行肉桂酰化分析。这些结果为真菌中PTM调控机制的进一步研究奠定了坚实基础，并有助于提高针对这些具有重要医学意义的物种的抗真菌策略。