title: Proteomic analysis of lysine succinylation of the human pathogen Histoplasma capsulatum.
abstract: 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.
  
  
  
  H. 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.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Longxiang
authors.initials: L
authors.lastname: Xie
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Wanyan
authors.initials: W
authors.lastname: Deng
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Zhaoxiao
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Fang
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liao
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China. Electronic address: georgex@swu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: panweihua@medmail.com.cn.
authors.forename: Weihua
authors.initials: W
authors.lastname: Pan
mesh_terms: D019295:Computational Biology; D005656:Fungal Proteins / Q000032:analysis* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006658:Histoplasma / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D019802:Succinic Acid / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D005656:Fungal Proteins; D006657:Histones; D019802:Succinic Acid; D008239:Lysine
keywords: Chaperone; Histone proteins; Lysine succinylation; Metabolism; Post-translational protein modification