Candida albicans is the most common human fungal pathogen, causing diseases ranging from mucosal to systemic infections for both immunocompetent and immunocompromised individuals. Lysine 2-hydroxyisobutyrylation is a highly conserved posttranslational modification found in a wide variety of organisms. In this study, we surveyed the biological impact of 2-hydroxyisobutyrylation on lysine residuals (Khib) in C. albicans. Using an antibody enrichment approach along with the traditional liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, we analyzed the pattern of Khib-modified proteins and sites in one wild-type strain of C. albicans. We identified 1,438 Khib-modified proteins with 6,659 modified sites in this strain, and a more detailed bioinformatics analysis indicated that the Khib-modified proteins are involved in a wide range of cellular functions with diverse subcellular locations. Functional enrichment analysis featured several prominent functional pathways, including ribosome, biosynthesis of antibiotics, biosynthesis of secondary metabolites, biosynthesis of amino acids and carbon metabolism, of which the ribosome pathway is the most affected pathway. Even compared with the reported numbers of lysine acetylation (Kac) and succinylation (Ksuc) sites, the numbers of Khib-modified sites on ribosomal proteins remained the highest for C. albicans. These bioinformatic results suggest that 2-hydroxyisobutyrylation may play an indispensable role in the regulation of the ribosomal biogenesis and protein translation. Findings in this study may provide new insights for studying posttranslational modification (PTM)-associated mechanisms in fungal development and pathogenicity.

中文翻译：

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白色念珠菌中赖氨酸2-羟基异丁酰化的蛋白质组学分析

白色念珠菌是最常见的人类真菌病原体，对免疫能力强和免疫功能低下的人造成从粘膜到全身感染的疾病。赖氨酸2-羟基异丁酰化是一种高度保守的翻译后修饰，存在于多种生物中。在这项研究中，我们调查了2-羟基异丁酰化对白色念珠菌赖氨酸残基（Khib）的生物学影响。使用抗体富集方法以及传统的液相色谱-串联质谱（LC-MS / MS）方法，我们分析了一株白色念珠菌的野生型菌株中Khib修饰的蛋白质的模式和位点。我们在该菌株中鉴定了1,438个具有6659个修饰位点的Khib修饰蛋白，更详细的生物信息学分析表明，Khib修饰的蛋白参与了范围广泛的具有不同亚细胞位置的细胞功能。功能富集分析具有几个突出的功能途径，包括核糖体，抗生素的生物合成，次生代谢产物的生物合成，氨基酸的生物合成和碳代谢，其中核糖体途径是受影响最大的途径。即使与报道的赖氨酸乙酰化（Kac）和琥珀酰化（Ksuc）位点的数量相比，核糖体蛋白上的Khib修饰位点的数量仍然是白色念珠菌的最高。这些生物信息学结果表明2-羟基异丁酰化可能在核糖体生物发生和蛋白质翻译的调节中起着不可或缺的作用。这项研究的发现可能为研究真菌发育和致病性的翻译后修饰（PTM）相关机制提供新的见解。