Proteomic analysis of lysine succinylation of the human pathogen Histoplasma capsulatum

Publication date: 10 February 2017
Source:Journal of Proteomics, Volume 154
Author(s): Longxiang Xie, Juan Li, Wanyan Deng, Zhaoxiao Yu, Wenjie Fang, Min Chen, Wanqing Liao, Jianping Xie, Weihua Pan
Histoplasma capsulatum, the causative agent of histoplasmosis (also called "Darling's disease"), can affect both immunocompetent and immunocompromised hosts. Post-translational protein modification by lysine succinylation (Ksuc) is a frequent occurrence in eukaryote and prokaryote. Recently, the roles of succinylation and its regulatory enzymes in regulating metabolic pathway in bacteria, mammalian and fungus were highlighted. Here, we report the first global profiling of lysine succinylation, with 463 modification sites in 202 proteins from H. capsulatum NAM1 identified, coupling immune-affinity enrichment using an anti-succinyllysine antibody with mass spectrometry. The bioinformatics results including GO functional and enrichment analysis showed that these succinylated proteins are mainly involved in central metabolism and protein synthesis, consistent with previous reports. 13 lysine succinylation sites on histones including H2A, H2B, H3 and H4 in H. capsulatum were firstly reported. The data is a good resource for further functional characterization of lysine succinylation in H. capsulatum.Biological significanceH. capsulatum is the causative agent of lung disease histoplasmosis. The ability of H. capsulatum yeasts to infect and proliferate within macrophages as an intracellular pathogen can be contributed to several virulence factors and metabolic regulation. Lysine succinylation was recently shown to play a critical role in the metabolism regulation of Candida albicans. H. capsulatum succinylated proteins were firstly characterized in this work, and bioinformatics results showed that this modification may also be relevant with central metabolism in H. capsulatum. New succinylation sites on histones were reported. This represents an important resource to address the function of H. capsulatum lysine succinylation.

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