Sage Journals: Discover world-class research

Abstract

Candida tropicalis belongs to the non-albicans group of Candida, and causes epidermal, mucosal, or systemic candidiasis in immunocompromised individuals. Although the prevalence of candidiasis has increased worldwide and non-albicans Candida (NAC) are becoming more significant, there are very few studies that focus on the NAC biology. Proteins and their post-translational modifications (PTMs) are an integral aspect in the pathobiology of such medically important fungi. Previously, we had reported the largest proteomic catalog of C. tropicalis. Notably, PTMs can be identified from proteomics data without a priori enrichment for a particular PTM, thus allowing broad-scale omics analyses. In this study, we developed the “PTM-Pro,” a graphical user interface-based tool for identification and summary of high-confidence PTM sites based on statistical threshold of users' choice. We mined available proteomic data of C. tropicalis, and using PTM-Pro identified nearly 600 high-confidence PTM sites. The PTMs identified include phosphorylation of serine, threonine, and tyrosine; acetylation, crotonylation, methylation, and succinylation of lysine. These PTMs reside on biologically significant molecules, including histones, enzymes, and transcription factors. To our knowledge, this is the first report of PTMs in C. tropicalis and lays a foundation for future investigations of C. tropicalis PTMs. In addition, the PTM-Pro offers a graphical user interface tool for research on PTM sites in the field of proteomics.

Get full access to this article

View all access options for this article.

References

Beausoleil

, Villen

, Gerber

, Rush

, and Gygi

. (2006). A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol, 24, 1285–1292.

Bennett

. (2010). Coming of age—Sexual reproduction in Candida species. PLoS Pathog, 6, e1001155.

Bhatia

, Perlman

, Costello

, and McComb

. (2009). Software tool for researching annotations of proteins: Open-source protein annotation software with data visualization. Anal Chem, 81, 9819–9823.

Brohi

, and Huo

. (2017). Posttranslational modifications in spermatozoa and effects on male fertility and sperm viability. OMICS, 21, 245–256.

Chick

, Kolippakkam

, Nusinow

, et al. (2015). A mass-tolerant database search identifies a large proportion of unassigned spectra in shotgun proteomics as modified peptides. Nat Biotechnol, 33, 743–749.

Creasy

, and Cottrell

. (2004). Unimod: Protein modifications for mass spectrometry. Proteomics, 4, 1534–1536.

Culibrk

, Croft

, and Tebbutt

. (2016). Systems biology approaches for host-fungal interactions: An expanding multi-omics frontier. OMICS, 20, 127–138.

Datta

, Patil

, Patel

, et al. (2016). Proteogenomics of Candida tropicalis—An opportunistic pathogen with importance for global health. OMICS, 20, 239–247.

Griss

, Perez-Riverol

, Lewis

, et al. (2016). Recognizing millions of consistently unidentified spectra across hundreds of shotgun proteomics datasets. Nat Methods, 13, 651–656.

10.

Groth

, Rocha

, Verreault

, and Almouzni

. (2007). Chromatin challenges during DNA replication and repair. Cell, 128, 721–733.

11.

Hornbeck

, Zhang

, Murray

, et al. (2015). PhosphoSitePlus, 2014: Mutations, PTMs and recalibrations. Nucleic Acids Res, 43, D512–D520.

12.

Hunter

. (1995). Protein kinases and phosphatases: The yin and yang of protein phosphorylation and signaling. Cell, 80, 225–236.

13.

Kall

, Canterbury

, Weston

, Noble

, and MacCoss

. (2007). Semi-supervised learning for peptide identification from shotgun proteomics datasets. Nat Methods, 4, 923–925.

14.

Kall

, Storey

, and Noble

. (2009). QVALITY: Non-parametric estimation of q-values and posterior error probabilities. Bioinformatics, 25, 964–966.

15.

Karve

, and Cheema

. (2011). Small changes huge impact: The role of protein posttranslational modifications in cellular homeostasis and disease. J Amino Acids, 2011, 207691.

16.

Kim

, Zhong

, and Pandey

. (2016). Common errors in mass spectrometry-based analysis of post-translational modifications. Proteomics, 16, 700–714.

17.

Kurdistani

, and Grunstein

. (2003). Histone acetylation and deacetylation in yeast. Nat Rev Mol Cell Biol, 4, 276–284.

18.

Leach

, and Brown

. (2012). Posttranslational modifications of proteins in the pathobiology of medically relevant fungi. Eukaryot Cell, 11, 98–108.

19.

Letunic

, Doerks

, and Bork

. (2015). SMART: Recent updates, new developments and status in 2015. Nucleic Acids Res, 43, D257–D260.

20.

, Carey

, and Workman

. (2007). The role of chromatin during transcription. Cell, 128, 707–719.

21.

, Agrellos

, and Calderone

. (2010). Histidine kinases keep fungi safe and vigorous. Curr Opin Microbiol, 13, 424–430.

22.

Lin

, Su

, and He

. (2012). Protein lysine acylation and cysteine succination by intermediates of energy metabolism. ACS Chem Biol, 7, 947–960.

23.

Martin

, and Zhang

. (2005). The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol, 6, 838–849.

24.

Mortensen

, Gouw

, Olsen

, et al. (2010). MSQuant, an open source platform for mass spectrometry-based quantitative proteomics. J Proteome Res, 9, 393–403.

25.

Nielsen

, Savitski

, and Zubarev

. (2006). Extent of modifications in human proteome samples and their effect on dynamic range of analysis in shotgun proteomics. Mol Cell Proteomics, 5, 2384–2391.

26.

Papon

, Courdavault

, Clastre

, and Bennett

. (2013). Emerging and emerged pathogenic Candida species: Beyond the Candida albicans paradigm. PLoS Pathog, 9, e1003550.

27.

Rakus

, and Mahal

. (2011). New technologies for glycomic analysis: Toward a systematic understanding of the glycome. Annu Rev Anal Chem (Palo Alto Calif), 4, 367–392.

28.

Sardi

, Scorzoni

, Bernardi

, Fusco-Almeida

, and Mendes Giannini

. (2013). Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J Med Microbiol, 62, 10–24.

29.

Schwartz

, and Gygi

. (2005). An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets. Nat Biotechnol, 23, 1391–1398.

30.

Taus

, Kocher

, Pichler

, et al. (2011). Universal and confident phosphorylation site localization using phosphoRS. J Proteome Res, 10, 5354–5362.

31.

Thompson

, Carlisle

, and Kadosh

. (2011). Coevolution of morphology and virulence in Candida species. Eukaryot Cell, 10, 1173–1182.

32.

Weinert

, Scholz

, Wagner

, et al. (2013). Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep, 4, 842–851.

33.

Wilkinson

. (1987). Protein ubiquitination: A regulatory post-translational modification. Anticancer Drug Des, 2, 211–229.

34.

Willger

, Liu

, Olarte

, et al. (2015). Analysis of the Candida albicans phosphoproteome. Eukaryot Cell, 14, 474–485.

35.

Xie

, Dai

, et al. (2012). Lysine succinylation and lysine malonylation in histones. Mol Cell Proteomics, 11, 100–107.

36.

Zheng

, He

, Zhou

, et al. (2016). Systematic analysis of the lysine succinylome in Candida albicans. J Proteome Res, 15, 3793–3801.

37.

Zhou

, Qian

, Yi

, Li

, and Liu

. (2016). Systematic analysis of the lysine acetylome in Candida albicans. J Proteome Res, 15, 2525–2536.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.15 MB

Dissecting Candida Pathobiology: Post-Translational Modifications on the Candida tropicalis Proteome

Abstract

Abstract

Get full access to this article

References

Supplementary Material