Table1_Proteome-Wide Identification and Functional Analysis of Lysine Crotonylation in Trichophyton rubrum Conidial and Mycelial Stages.XLSX

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.

赖氨酸肉豆蔻酰化是一种新近发现的翻译后修饰（PTM），其在多种重要的调控通路中扮演着核心角色。尽管其功能意义显著，但对于真菌中肉豆蔻酰化的了解仍然有限。红色毛癣菌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，我们获得了红色毛癣菌的全蛋白质组肉豆蔻酰化谱，从而鉴定出3144种蛋白质上的14,019个肉豆蔻酰化位点。肉豆蔻酰化蛋白质在翻译以及多种代谢和生物合成过程中显著参与。此外，一些与真菌致病性相关的蛋白质也被发现是肉豆蔻酰化的靶点。此外，组蛋白上的广泛肉豆蔻酰化表明其在表观遗传调控中发挥作用。进一步地，大约一半的肉豆蔻酰化蛋白质特异性地存在于分生孢子或菌丝阶段，功能富集分析显示出这两个阶段之间的某些差异。结果表明，两个阶段之间肉豆蔻酰化的差异并非由蛋白质丰度差异引起。肉豆蔻酰化与乙酰化、丙酰化和琥珀酰化的串扰表明其具有不同的调控作用。本研究是首次在皮肤癣菌和人类致病性丝状真菌中进行的肉豆蔻酰化分析。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，并应有助于提高针对这些医学重要物种的抗真菌策略。