Relevance and proteomics challenge of functional posttranslational modifications in Kinetoplastid parasites

K. Pisarski, The Global Burden of Disease of Zoonotic Parasitic Diseases: Top 5 Contenders for Priority Consideration, Trop. Med. Infect. Dis., 2;4(1). (2019) pii: E44. Custodio, 2016, Protozoan Parasites, Pediatr. Rev., 37, 59, 10.1542/pir.2015-0006 M. Recker, P.C. Bull, C.O. Buckee, Recent advances in the molecular epidemiology of clinical malaria, F1000Res., 30;7 (2018) pii: F1000 Faculty Rev-1159. Pramanik, 2019, Drug resistance in protozoan parasites: an incessant wrestle for survival, J Glob Antimicrob Resist., 18, 1, 10.1016/j.jgar.2019.01.023 Caljon, 2016, Alice in microbes' land: adaptations and counter-adaptations of vector-borne parasitic protozoa and their hosts, FEMS Microbiol. Rev., 5, 664, 10.1093/femsre/fuw018 M. Recker, P.C. Bull, C.O. Buckee, Recent advances in the molecular epidemiology of clinical malaria, F1000Res., 7 (2018) pii: F1000 Faculty Rev-1159. Sundar, 2018, Understanding Leishmania parasites through proteomics and implications for the clinic, Expert Rev Proteomics., 15, 371, 10.1080/14789450.2018.1468754 S.C. Charnaud, T.K. Jonsdottir, P.R. Sanders, H.E. Bullen, B.K. Dickerman, B. Kouskousis, C.S. Palmer, H.M. Pietrzak, A.E. Laumaea, A.B. Erazo, E. McHugh E, L. Tilley, B.S. Crabb, P.R. Gilson, Spatial organization of protein export in malaria parasite blood stages, Traffic., 19(8) (2018), 605–623. Fernández-Moya, 2010, Posttranscriptional control and the role of RNA-binding proteins in gene regulation in trypanosomatid protozoan parasites, Wiley Interdiscip Rev RNA., 1, 34, 10.1002/wrna.6 Yakubu, 2018, Post-translational modifications as key regulators of apicomplexan biology: insights from proteome-wide studies, Mol. Microbiol., 107, 1, 10.1111/mmi.13867 Millar, 2019, The scope, functions, and dynamics of posttranslational protein modifications, Annu. Rev. Plant Biol., 70, 119, 10.1146/annurev-arplant-050718-100211 Ke, 2016, Identification, quantification, and site localization of protein posttranslational modifications via mass spectrometry-based proteomics, Adv. Exp. Med. Biol., 919, 345, 10.1007/978-3-319-41448-5_17 Greco, 2016, The biochemical evolution of protein complexes, Trends Biochem. Sci., 41, 4, 10.1016/j.tibs.2015.11.007 Wozniak, 2019, PTMphinder: an R package for PTM site localization and motif extraction from proteomic datasets, PeerJ., 7, 10.7717/peerj.7046 F. Li, C. Fan, T.T. Marquez-Lago, A. Leier, J. Revote, C. Jia, Y. Zhu, A.I. Smith, G.I. Webb, Q. Liu, L. Wei, J. Li, J. Song, PRISMOID: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact, Brief Bioinform., (2019) pii: bbz050. Li, 2017, Global post-translational modification discovery, J. Proteome Res., 16, 1383, 10.1021/acs.jproteome.6b00034 Niimi, 2016, Leishmania tarentolae for the production of multi-subunit complexes, Adv. Exp. Med. Biol., 896, 155, 10.1007/978-3-319-27216-0_10 Vincenzi, 2019, Protein interaction domains and post-translational modifications: structural features and drug discovery applications, Curr. Med. Chem., 10.2174/0929867326666190620101637 Pejaver, 2014, The structural and functional signatures of proteins that undergo multiple events of post-translational modification, Protein Sci., 23, 1077, 10.1002/pro.2494 Salomon, 2013, What pathogens have taught us about posttranslational modifications, Cell Host Microbe, 14, 269, 10.1016/j.chom.2013.07.008 Liu, 2016, Post-translational modification control of innate immunity, Immunity., 45, 15, 10.1016/j.immuni.2016.06.020 Mahanta, 2018, Integrative approaches to understand the mastery in manipulation of host cytokine networks by protozoan parasites with emphasis on Plasmodium and Leishmania species, Front. Immunol., 9, 296, 10.3389/fimmu.2018.00296 Arnold, 2018, Prospects from systems serology research, Immunology., 153, 279, 10.1111/imm.12861 Filardy, 2018, Human Kinetoplastid protozoan infections: where are we going next?, Front. Immunol., 9, 1493, 10.3389/fimmu.2018.01493 Malaney, 2017, PTEN proteoforms in biology and disease, Cell. Mol. Life Sci., 74, 2783, 10.1007/s00018-017-2500-6 H. Ryšlavá, V. Doubnerová, D. Kavan, O. Vaněk O, Effect of posttranslational modifications on enzyme function and assembly, J Proteomics., 92 (2013), 80–109. Sirota, 2015, Single-residue posttranslational modification sites at the N-terminus, C-terminus or in-between: to be or not to be exposed for enzyme access Proteomics, 15, 2525 S. Jaisson, P. Gillery Evaluation of nonenzymatic posttranslational modification-derived products as biomarkers of molecular aging of proteins. Clin Chem, 56 (2010), pp. 1401–1412. Harmel, 2018, Features and regulation of non-enzymatic post-translational modifications, Nat. Chem. Biol., 14, 244, 10.1038/nchembio.2575 Berezovsky, 2017, Protein function machinery: from basic structural units to modulation of activity, Curr. Opin. Struct. Biol., 42, 67, 10.1016/j.sbi.2016.10.021 Eichler, 2005, Posttranslational protein modification in Archaea, Microbiol. Mol. Biol. Rev., 69, 393, 10.1128/MMBR.69.3.393-425.2005 Karlaftis, 2016, Importance of post-translational modifications on the function of key haemostatic proteins, Blood Coagul. Fibrinolysis, 27, 1, 10.1097/MBC.0000000000000301 Baker, 2017, Posttranslational modification as a critical determinant of cytoplasmic innate immune recognition, Physiol. Rev., 97, 1165, 10.1152/physrev.00026.2016 Liu, 2016, Post-translational modification control of innate immunity, Immunity., 45, 15, 10.1016/j.immuni.2016.06.020 Duran-Bedolla, 2017, Cellular stress associated with the differentiation of Plasmodium berghei ookinetes, Biochem. Cell Biol., 95, 310, 10.1139/bcb-2016-0028 Jean Beltran, 2017, Proteomics and integrative omic approaches for understanding host-pathogen interactions and infectious diseases, Mol. Syst. Biol., 13, 922, 10.15252/msb.20167062 Salomon, 2013, Lost after translation: post-translational modifications by bacterial type III effectors, Curr. Opin. Microbiol., 16, 213, 10.1016/j.mib.2013.01.013 Chiang, 2017, Post-translational control of intracellular pathogen sensing pathways, Trends Immunol., 38, 39, 10.1016/j.it.2016.10.008 Duan, 2015, The roles of post-translational modifications in the context of protein interaction networks, PLoS Comput. Biol., 11, 10.1371/journal.pcbi.1004049 Krassowski, 2018, ActiveDriverDB: human disease mutations and genome variation in post-translational modification sites of proteins, Nucleic Acids Res., 46, D901, 10.1093/nar/gkx973 Walsh, 2005, Gatto, protein posttranslational modifications: the chemistry of proteome diversifications, Angew. Chem. Int. Ed. Engl., 44, 7342, 10.1002/anie.200501023 Basak, 2016, Post-translational protein modifications of rare and unconventional types: implications in functions and diseases, Curr. Med. Chem., 23, 714, 10.2174/0929867323666160118095620 UniProt Consortium T1,2,3,4. UniProt: the universal protein knowledgebase. Mowen, 2014, Unconventional post-translational modifications in immunological signaling, Nat. Immunol., 15, 512, 10.1038/ni.2873 Vu, 2018, Protein language: post-translational modifications talking to each other, Trends Plant Sci., 23, 1068, 10.1016/j.tplants.2018.09.004 Yakubu, 2018, Post-translational modifications as key regulators of apicomplexan biology: insights from proteome-wide studies, Mol. Microbiol., 107, 1, 10.1111/mmi.13867 Conradi, 2018, Dynamics of posttranslational modification systems: recent Progress and future directions, Biophys. J., 114, 507, 10.1016/j.bpj.2017.11.3787 Venne, 2014, The next level of complexity: crosstalk of posttranslational modifications, Proteomics., 14, 513, 10.1002/pmic.201300344 Csizmok, 2018, Complex regulatory mechanisms mediated by the interplay of multiple post-translational modifications, Curr. Opin. Struct. Biol., 48, 58, 10.1016/j.sbi.2017.10.013 K.Y. Huang, T.Y. Lee, H.J. Kao, C.T. Ma, C.C. Lee, T.H. Lin, W.C. Chang, H.D. Huang, dbPTM in 2019: exploring disease association and cross-talk of post-translational modifications, Nucleic. Acids. Res., 47(D1) (2019), D298-D308. Tran, 2019, Engineering proteases for mass spectrometry-based post translational modification analyses, Proteomics., 19, 10.1002/pmic.201700471 Melo-Braga, 2015, Comprehensive protocol to simultaneously study protein phosphorylation, acetylation, and N-linked sialylated glycosylation, Methods Mol. Biol., 1295, 275, 10.1007/978-1-4939-2550-6_21 Yakubu, 2019, The methods employed in mass spectrometric analysis of posttranslational modifications (PTMs) and protein–protein interactions (PPIs), Adv. Exp. Med. Biol., 1140, 169, 10.1007/978-3-030-15950-4_10 D. Pascovici, J.X. Wu, M.J. McKay, C. Joseph, Z. Noor, K. Kamath, Y. Wu, S. Ranganathan, V. Gupta, M. Mirzaei, Clinically Relevant Post-Translational Modification Analyses-Maturing Workflows and Bioinformatics Tools, Int. J. Mol. Sci., 20(1) (2018), pii: E16. Aslebagh, 2019, Identification of posttranslational modifications (PTMs) of proteins by mass spectrometry, Adv. Exp. Med. Biol., 1140, 199, 10.1007/978-3-030-15950-4_11 Calderón-Celis, 2018, Standardization approaches in absolute quantitative proteomics with mass spectrometry, Mass Spectrom. Rev., 37, 715, 10.1002/mas.21542 Neiswinger, 2016, Posttranslational modification assays on functional protein microarrays, Cold Spring Harb Protoc, 10 Gianazza, 2018, Post-translational quantitation by SRM/MRM: applications in cardiology, Expert. Rev. Proteomics., 15, 477, 10.1080/14789450.2018.1484283 Li, 2017, Global post-translational modification discovery, J. Proteome Res., 16, 1383, 10.1021/acs.jproteome.6b00034 LeDuc, 2018, ProForma: a standard Proteoform notation, J. Proteome Res., 17, 1321, 10.1021/acs.jproteome.7b00851 Schaffer, 2019, Identification and quantification of Proteoforms by mass spectrometry, Proteomics., 19 Schaffer, 2018, Expanding Proteoform identifications in top-down proteomic analyses by constructing Proteoform families, Anal. Chem., 90, 1325, 10.1021/acs.analchem.7b04221 H. Horita, A. Law, K. Middleton, Utilizing Optimized Tools to Investigate PTM Crosstalk: Identifying Potential PTM Crosstalk of Acetylated Mitochondrial Proteins, Proteomes., 6(2) (2018), pii: E24. Stetz, 2018, Dissecting structure-encoded determinants of allosteric Cross-talk between post-translational modification sites in the Hsp90 chaperones, Sci. Rep., 8, 6899, 10.1038/s41598-018-25329-4 Eisenberg-Lerner, 2016, Post-translational modification profiling - a novel tool for mapping the protein modification landscape in cancer, Exp Biol Med (Maywood)., 241, 1475, 10.1177/1535370216651732 Ivry, 2018, Global substrate specificity profiling of post-translational modifying enzymes, Protein Sci., 27, 584, 10.1002/pro.3352 H. Chen, S. Venkat, P. McGuire, Q. Gan, C. Fan, Recent Development of Genetic Code Expansion for Posttranslational Modification Studies, Molecules., 23(7) (2018), pii: E1662. Venkat, 2019, The application of cell-free protein synthesis in genetic code expansion for post-translational modifications, Front. Pharmacol., 10, 248, 10.3389/fphar.2019.00248 Pinto, 2019, Functional proteomic analysis to characterize signaling crosstalk, Methods Mol. Biol., 1871, 197, 10.1007/978-1-4939-8814-3_14 Chaudhuri, 2017, Cross-species PTM mapping from Phosphoproteomic data, Methods Mol. Biol., 1558, 459, 10.1007/978-1-4939-6783-4_22 Callahan, 2020, Strategies for development of a next-generation protein sequencing platform, Trends Biochem. Sci., 45, 76, 10.1016/j.tibs.2019.09.005 Kim, 2016, Common errors in mass spectrometry-based analysis of post-translational modifications, Proteomics., 16, 700, 10.1002/pmic.201500355 Skinner, 2015, Illuminating the dark matter of shotgun proteomics, Nat. Biotechnol., 33, 717, 10.1038/nbt.3287 P. Minguez, P. Bork P, Bioinformatics Analysis of Functional Associations of PTMs, Methods. Mol. Biol., 1558 (2017) 303–320. Devabhaktuni, 2019, TagGraph reveals vast protein modification landscapes from large tandem mass spectrometry datasets, Nat. Biotechnol., 37, 469, 10.1038/s41587-019-0067-5 Tiwari, 2019, Post-translational modification of ESKAPE pathogens as a potential target in drug discovery, Drug Discov. Today, 24, 814, 10.1016/j.drudis.2018.12.005 Szöör, 2010, Trypanosomatid protein phosphatases, Mol. Biochem. Parasitol., 173, 53, 10.1016/j.molbiopara.2010.05.017 Mittal, 2013, Unique posttranslational modifications in eukaryotic translation factors and their roles in protozoan parasite viability and pathogenesis, Mol. Biochem. Parasitol., 187, 21, 10.1016/j.molbiopara.2012.11.001 Jortzik, 2012, Thiol-based posttranslational modifications in parasites, Antioxid. Redox Signal., 17, 657, 10.1089/ars.2011.4266 Rosenzweig, 2008, Post-translational modification of cellular proteins during Leishmania donovani differentiation, Proteomics., 8, 1843, 10.1002/pmic.200701043 Urbaniak, 2013, Global quantitative SILAC phosphoproteomics reveals differential phosphorylation is widespread between the procyclic and bloodstream form lifecycle stages of Trypanosoma brucei, J. Proteome Res., 12, 2233, 10.1021/pr400086y Leznicki, 2017, Mechanisms of regulation and diversification of deubiquitylating enzyme function, J. Cell Sci., 130, 1997, 10.1242/jcs.201855 M. Staszczak, [Ubiquitin-proteasome pathway as a target for therapeutic strategies], Postepy Biochem., 63(4) (2017), 287–303. Fiorillo, 2014, The crystal structure of Giardia duodenalis 14-3-3 in the apo form: when protein post-translational modifications make the difference, PLoS One, 9, 10.1371/journal.pone.0092902 Lott, 2013, Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation, J. Proteome, 91, 210, 10.1016/j.jprot.2013.07.010 Paluszynski, 2014, Biochemical and functional characterization of CpMuc4, a Cryptosporidium surface antigen that binds to host epithelial cells, Mol. Biochem. Parasitol., 193, 114, 10.1016/j.molbiopara.2014.03.005 Shiels, 1995, Selection of diversity at putative glycosylation sites in the immunodominant merozoite/piroplasm surface antigen of Theileria parasites, Mol. Biochem. Parasitol., 72, 149, 10.1016/0166-6851(95)00074-B Brown, 2017, Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence, Crit. Rev. Biochem. Mol. Biol., 52, 145, 10.1080/10409238.2017.1287161 Reiter, 2013, Identification of biochemically distinct properties of the small ubiquitin-related modifier (SUMO) conjugation pathway in Plasmodium falciparum, J. Biol. Chem., 288, 27724, 10.1074/jbc.M113.498410 Casanova, 2015, Characterisation of polyglutamylases in trypanosomatids, Int. J. Parasitol., 45, 121, 10.1016/j.ijpara.2014.09.005 Conradi, 2018, Dynamics of posttranslational modification systems: recent Progress and future directions, Biophys. J., 114, 507, 10.1016/j.bpj.2017.11.3787 T. Suwanmajo, J. Krishnan, Exploring the intrinsic behaviour of multisite phosphorylation systems as part of signalling pathways, J R Soc Interface., 15(143) (2018), pii: 20180109. Field, 2017, Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need, Nat. Rev. Microbiol., 15, 217, 10.1038/nrmicro.2016.193 J. Alvar, I.D. Vélez, C. Bern, M. Herrero, P. Desjeux, J. Cano, J. Jannin, M. Boer, the WHO Leishmaniasis Control Team, Leishmaniasis worldwide and global estimates of its incidence., PLoS One., 7(5) (2012), e35671. Kennedy, 2019, Update on human African trypanosomiasis (sleeping sickness), J. Neurol., 266, 2334, 10.1007/s00415-019-09425-7 Guha, 2014, Lys-413 of S-phase mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) is modified through monoubiquitination that is responsible for inhibition of its riboendonuclease activity, Indian J. Biochem. Biophys., 51, 559 Liao, 2010, The small ubiquitin-like modifier (SUMO) is essential in cell cycle regulation in Trypanosoma brucei, Exp. Cell Res., 316, 704, 10.1016/j.yexcr.2009.12.017 Liao, 2017, The protein Neddylation pathway in Trypanosoma brucei: functional characterization and substrate identification, J. Biol. Chem., 292, 1081, 10.1074/jbc.M116.766741 Lott, 2013, Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation, J. Proteome, 91, 210, 10.1016/j.jprot.2013.07.010 L. Basmaciyan, D.R. Robinson, N. Azas, M. Casanova, (De)glutamylation and cell death in Leishmania parasites, PLoS Negl Trop Dis., 13(4) (2019), e0007264. Pereira, 2015, Down regulation of NO signaling in Trypanosoma cruzi upon parasite-extracellular matrix interaction: changes in protein modification by nitrosylation and nitration, PLoS Negl. Trop. Dis., 9, 10.1371/journal.pntd.0003683 S. Hem, P.F. Gherardini, J. Osorio y Fortéa, V. Hourdel, M.A. Morales, et al, Identification of Leishmania-specific protein phosphorylation sites by LC-ESI-MS/MS and comparative genomics analyses, Proteomics., 10(21) (2010) 3868–83. Tsigankov, 2014, Regulation dynamics of Leishmania differentiation: deconvoluting signals and identifying phosphorylation trends, Mol. Cell. Proteomics, 13, 1787, 10.1074/mcp.M114.037705 Avila, 2016, Phosphorylation of eIF2α on threonine 169 is not required for Trypanosoma brucei cell cycle arrest during differentiation, Mol. Biochem. Parasitol., 205, 16, 10.1016/j.molbiopara.2016.03.004 O.P de Melo Neto, T.D. da Costa Lima, C.C. Xavier, L.M. Nascimento, T.P. Romão, L.A. Assis, M.M. Pereira, C.R. Reis, B. Papadopoulou, The unique Leishmania EIF4E4 N-terminus is a target for multiple phosphorylation events and participates in critical interactions required for translation initiation, RNA Biol., 12(11) (2015), 1209–21. de Melo Neto, 2018, Phosphorylation and interactions associated with the control of the Leishmania poly-a binding protein 1 (PABP1) function during translation initiation, RNA Biol., 15, 739 K. Abhishek, A.H. Sardar, S. Das, A. Kumar, A.K. Ghosh, R. Singh, S. Saini, A. Mandal, S. Verma, A. Kumar, B. Purkait, M.R. Dikhit, P. Das, Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival, Mol Cell Biol., 37(1) (2016), pii: e00344–16. Rocha, 2014, Stress induces changes in the phosphorylation of Trypanosoma cruzi RNA polymerase II, affecting its association with chromatin and RNA processing, Eukaryot. Cell, 13, 855, 10.1128/EC.00066-14 Lucena, 2019, Quantitative phosphoproteome and proteome analyses emphasize the influence of phosphorylation events during the nutritional stress of Trypanosoma cruzi: the initial moments of in vitro metacyclogenesis, Cell Stress Chaperones, 24, 927, 10.1007/s12192-019-01018-7 R. Hope, E. Ben-Mayor, N. Friedman, K. Voloshin, D. Biswas, D. Matas, Y. Drori, A. Günzl, S. Michaeli, Phosphorylation of the TATA-binding protein activates the spliced leader silencing pathway in Trypanosoma brucei, Sci Signal., 7(341) (2014), ra85. Bhandari, 2014, Elucidation of cellular mechanisms involved in experimental paromomycin resistance in Leishmania donovani, Antimicrob. Agents Chemother., 58, 2580, 10.1128/AAC.01574-13 Gutiérrez-Corbo, 2019, Topoisomerase IB poisons induce histone H2A phosphorylation as a response to DNA damage in Leishmania infantum, Int. J. Parasitol. Drugs Drug Resist., 11, 39, 10.1016/j.ijpddr.2019.09.005 Maldonado, 2015, Expression, purification, and biochemical characterization of recombinant DNA polymerase beta of the Trypanosoma cruzi TcI lineage: requirement of additional factors and detection of phosphorylation of the native form, Parasitol. Res., 114, 1313, 10.1007/s00436-014-4308-8 Norris-Mullins, 2018, Leishmania phosphatase PP5 is a regulator of HSP83 phosphorylation and essential for parasite pathogenicity, Parasitol. Res., 117, 2971, 10.1007/s00436-018-5994-4 Mattos, 2012, Adhesion of Trypanosoma cruzi trypomastigotes to fibronectin or laminin modifies tubulin and paraflagellar rod protein phosphorylation, PLoS One, 7, 10.1371/journal.pone.0046767 de Graffenried, 2013, Polo-like kinase phosphorylation of bilobe-resident TbCentrin2 facilitates flagellar inheritance in Trypanosoma brucei, Mol. Biol. Cell, 24, 1947, 10.1091/mbc.e12-12-0911 Yau, 2014, The Leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status, Mol. Microbiol., 93, 80, 10.1111/mmi.12639 Afrin, 2019, Leishmania-host interactions-an epigenetic paradigm, Front. Immunol., 10, 492, 10.3389/fimmu.2019.00492 Picchi, 2017, Post-translational modifications of Trypanosoma cruzi canonical and variant histones, J. Proteome Res., 16, 1167, 10.1021/acs.jproteome.6b00655 Picchi, 2017, Post-translational modifications of Trypanosoma cruzi canonical and variant histones, J. Proteome Res., 16, 1167, 10.1021/acs.jproteome.6b00655 Jha, 2017, HAT2 mediates histone H4K4 acetylation and affects micrococcal nuclease sensitivity of chromatin in Leishmania donovani, PLoS One, 12, 10.1371/journal.pone.0177372 T. Kawahara, T.N. Siegel, A.K. Ingram, S. Alsford, G.A. Cross, et al Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes, Mol Microbiol., 69 (2008), 1054–1068. Yadav, 2016, Histone acetyltransferase HAT4 modulates navigation across G2/M and re-entry into G1 in Leishmania donovani, Sci. Rep., 6, 27510, 10.1038/srep27510 Chandra, 2017, Cell cycle stage-specific transcriptional activation of cyclins mediated by HAT2-dependent H4K10 acetylation of promoters in Leishmania donovani, PLoS Pathog., 13, 10.1371/journal.ppat.1006615 Mahanta, 2018, Integrative approaches to understand the mastery in manipulation of host cytokine networks by protozoan parasites with emphasis on Plasmodium and Leishmania species, Front. Immunol., 9, 296, 10.3389/fimmu.2018.00296 Chen, 2018, Protein Lipidation in cell signaling and diseases: function, regulation, and therapeutic opportunities, Cell Chem Biol., 25, 817, 10.1016/j.chembiol.2018.05.003 Price, 2010, Myristoyl-CoA:protein N-myristoyltransferase depletion in trypanosomes causes avirulence and endocytic defects, Mol. Biochem. Parasitol., 169, 55, 10.1016/j.molbiopara.2009.09.006 Roberts, 2016, The N-myristoylome of Trypanosoma cruzi, Sci. Rep., 6, 31078, 10.1038/srep31078 Price, 2005, Functional analysis of TbARL1, an N-myristoylated Golgi protein essential for viability in bloodstream trypanosomes, J. Cell Sci., 118, 831, 10.1242/jcs.01624 Brown, 2017, Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence, Crit. Rev. Biochem. Mol. Biol., 52, 145, 10.1080/10409238.2017.1287161 Lander, 2015, CRISPR/Cas9-induced disruption of Paraflagellar rod protein 1 and 2 genes in Trypanosoma cruzi reveals their role in Flagellar attachment, MBio., 6, 10.1128/mBio.01012-15 Bhardwaj, 2017, Evaluation of CAAX prenyl protease II of Leishmania donovani as potential drug target: infectivity and growth of the parasite is significantly lowered after the gene knockout, Eur. J. Pharm. Sci., 102, 156, 10.1016/j.ejps.2017.03.005 E.K. Kruzel, G.P. Zimmett, 3rd, Bangs JD Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in Trypanosoma brucei, mSphere. 2(4) (2017), pii: e00282–17. Abbasnia, 2018, Isolation and purification of glycosylphosphatidylinositols (GPIs) in the schizont stage of Theileria annulata and determination of antibody response to GPI anchors in vaccinated and infected animals, Parasit. Vectors, 11, 82, 10.1186/s13071-018-2651-9 B. Mbengue, B. Niang, M.S. Niang, M.L. Varela, B. Fall et Al, Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis, Immun Inflamm Dis., 4(1) (2015), 24–34. De Pablos, 2012, Multigene families in Trypanosoma cruzi and their role in infectivity, Infect. Immun., 80, 2258, 10.1128/IAI.06225-11 Lantos, 2016, Sialic acid Glycobiology unveils Trypanosoma cruzi Trypomastigote membrane physiology, PLoS Pathog., 12, 10.1371/journal.ppat.1005559 G. Carlevaro, A.B. Lantos, G.E. Cánepa, M. de Los Milagros Cámara, M. Somoza et Al, Metabolic Labeling of Surface Neo-sialylglyconjugates Catalyzed by Trypanosoma cruzi trans-Sialidase, Methods Mol Biol., 1955 (2019), 135–146. Koeller, 2014, Golgi UDP-GlcNAc:polypeptide O-α-N-acetyl-d-glucosaminyltransferase 2 (TcOGNT2) regulates trypomastigote production and function in Trypanosoma cruzi, Eukaryot. Cell, 13, 1312, 10.1128/EC.00165-14 Cámara, 2019, Trypanosoma cruzi surface mucins are involved in the attachment to the Triatoma infestans rectal ampoule, PLoS Negl. Trop. Dis., 13, 10.1371/journal.pntd.0007418 Butkinaree, 2010, O-linked beta-N-acetylglucosamine (O-GlcNAc): extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress, Biochim. Biophys. Acta, 1800, 96, 10.1016/j.bbagen.2009.07.018 Torres-Gutiérrez, 2019, Identification of O-Glcnacylated proteins in Trypanosoma cruzi, Front Endocrinol (Lausanne)., 10, 199, 10.3389/fendo.2019.00199 García-Sánchez, 2014, Functional role of evolutionarily highly conserved residues, N-glycosylation level and domains of the Leishmania miltefosine transporter-Cdc50 subunit, Biochem. J., 459, 83, 10.1042/BJ20131318 Mondelaers, 2016, Genomic and molecular characterization of Miltefosine resistance in Leishmania infantum strains with either natural or acquired resistance through experimental selection of intracellular Amastigotes, PLoS One, 11, 10.1371/journal.pone.0154101