What is Known About N-Alpha Terminal Acetylation in Kinetoplastida Organisms
Main Article Content
Abstract
Nα-terminal acetylation (Nt-acetylation) is a conserved post-translational modification that plays an important role in stabilizing, localizing, and performing protein functions in general. Among kinetoplastid parasites such as species of Trypanosoma and Leishmania however, little work has been done to understand the role that this type of modification plays despite possessing an Nα-terminal acetylation machinery with unique N-terminal acetyltransferases. Particularly, since Nt-acetylation is important in stabilizing several key proteins that participate in various cellular processes, Nt-acetylation could be influencing parasite biology such as host-parasite interactions, establishment of different ecological niches, and general pathogenicity. The diverse roles that Nt-acetylation could be playing within kinetoplastids, given their complex life cycles and interactions with hosts, could be important. It is possible that the acetylation machinery, because of such kintoplastid-specific adaptations, represents an attractive target for therapeutic intervention. The unique aspects of Nt-acetylation in kinetoplastids can allow for further understanding of their biology along with innovative approaches for the treatment of pathogenic protozoans. Future studies should address the substrates, functional relevance, and druggability of Nt-acetylation in kinetoplastids to fill knowledge gaps, while also paving the path towards target-oriented drug development.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Aksnes H, Ree R, Arnesen T. Co-translational, Post-translational, and Non-catalytic Roles of N-Terminal Acetyltransferases. Molecular Cell. 2019 Mar;73(6):1097–114.
Pożoga M, Armbruster L, Wirtz M. From Nucleus to Membrane: A Subcellular Map of the N-Acetylation Machinery in Plants. IJMS. 2022 Nov 21;23(22):14492.
Ochaya S, Franzén O, Buhwa DA, Foyn H, Butler CE, Stove SI, et al. Characterization of Evolutionarily Conserved Trypanosoma cruzi NatC and NatA-N-Terminal Acetyltransferase Complexes. Journal of Parasitology Research. 2019 Mar 6;2019:1–11.
Ochaya S. Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections. In: El-Ashram S, Alouffi A, Dkhil M, editors. Infectious Diseases [Internet]. IntechOpen; 2024 [cited 2024 Dec 15]. Available from: https://www.intechopen.com/chapters/88629
Maran SR, Fleck K, Monteiro-Teles NM, Isebe T, Walrad P, Jeffers V, et al. Protein acetylation in the critical biological processes in protozoan parasites. Trends in Parasitology. 2021 Sep;37(9):815–30.
Chang YH. Impact of Protein Nα-Modifications on Cellular Functions and Human Health. Life. 2023 Jul 24;13(7):1613.
Constantinou M, Klavaris A, Koufaris C, Kirmizis A. Cellular effects of NAT-mediated histone N-terminal acetylation. Journal of Cell Science. 2023 Apr 1;136(7):jcs260801.
Clayton C, Shapira M. Post-transcriptional regulation of gene expression in trypanosomes and leishmanias. Molecular and Biochemical Parasitology. 2007 Dec;156(2):93–101.
Clayton C. Gene expression in Kinetoplastids. Current Opinion in Microbiology. 2016 Aug;32:46–51.
Drazic A, Myklebust LM, Ree R, Arnesen T. The world of protein acetylation. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 2016 Oct;1864(10):1372–401.
Guzman UH, Aksnes H, Ree R, Krogh N, Jakobsson ME, Jensen LJ, et al. Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae. Nat Commun. 2023 Jul 27;14(1):4517.
Alm Rosenblad M, López MD, Samuelsson T. The enigmatic RNase MRP of kinetoplastids. RNA Biology. 2021 Oct 15;18(sup1):139–47.
Ree R, Varland S, Arnesen T. Spotlight on protein N-terminal acetylation. Exp Mol Med. 2018 Jul;50(7):1–13.
Filardy AA, Guimarães-Pinto K, Nunes MP, Zukeram K, Fliess L, Pereira L, et al. Human Kinetoplastid Protozoan Infections: Where Are We Going Next? Front Immunol. 2018 Jul 25;9:1493.
Stuart K, Brun R, Croft S, Fairlamb A, Gürtler RE, McKerrow J, et al. Kinetoplastids: related protozoan pathogens, different diseases. J Clin Invest. 2008 Apr 1;118(4):1301–10.
Zhu R, Chen M, Luo Y, Cheng H, Zhao Z, Zhang M. The role of N-acetyltransferases in cancers. Gene. 2024 Jan;892:147866.
Stuart K, Brun R, Croft S, Fairlamb A, Gürtler RE, McKerrow J, et al. Kinetoplastids: related protozoan pathogens, different diseases. J Clin Invest. 2008 Apr 1;118(4):1301–10.
Lukeš J, Lys Guilbride D, Votýpka J, Zíková A, Benne R, Englund PT. Kinetoplast DNA Network: Evolution of an Improbable Structure. Eukaryot Cell. 2002 Aug;1(4):495–502.
Dean S. Basic Biology of Trypanosoma brucei with Reference to the Development of Chemotherapies. CPD. 2021 Apr;27(14):1650–70.
Romero-Meza G, Mugnier MR. Trypanosoma brucei. Trends in Parasitology. 2020 Jun;36(6):571–2.
Zuma AA, Dos Santos Barrias E, De Souza W. Basic Biology of Trypanosoma cruzi. CPD. 2021 Apr;27(14):1671–732.
Burza S, Croft SL, Boelaert M. Leishmaniasis. The Lancet. 2018 Sep;392(10151):951–70.
Mann S, Frasca K, Scherrer S, Henao-Martínez AF, Newman S, Ramanan P, et al. A Review of Leishmaniasis: Current Knowledge and Future Directions. Curr Trop Med Rep. 2021 Jun;8(2):121–32.
Kelly FD, Sanchez MA, Landfear SM. Touching the Surface: Diverse Roles for the Flagellar Membrane in Kinetoplastid Parasites. Microbiol Mol Biol Rev. 2020 May 20;84(2):e00079-19.
Halliday C, De Castro-Neto A, Alcantara CL, Cunha-e-Silva NL, Vaughan S, Sunter JD. Trypanosomatid Flagellar Pocket from Structure to Function. Trends in Parasitology. 2021 Apr;37(4):317–29.
Crowe LP, Morris MT. Glycosome heterogeneity in kinetoplastids. Biochemical Society Transactions. 2021 Feb 26;49(1):29–39.
Barros-Alvarez X, Gualdron-Lopez M, Acosta H, Caceres AJ, Graminha MAS, Michels PAM, et al. Glycosomal Targets for Anti-Trypanosomatid Drug Discovery. CMC. 2014 Apr 31;21(15):1679–706.
Elmahallawy EK, Alkhaldi AAM. Insights into Leishmania Molecules and Their Potential Contribution to the Virulence of the Parasite. Veterinary Sciences. 2021 Feb 20;8(2):33.
Devsani N, Vemula D, Bhandari V. The glycoprotein gp63– a potential pan drug target for developing new antileishmanial agents. Biochimie. 2023 Apr;207:75–82.
Cámara MDLM, Cánepa GE, Lantos AB, Balouz V, Yu H, Chen X, et al. The Trypomastigote Small Surface Antigen (TSSA) regulates Trypanosoma cruzi infectivity and differentiation. Burleigh BA, editor. PLoS Negl Trop Dis. 2017 Aug 11;11(8):e0005856.
Leão AC, Viana LA, Fortes De Araujo F, De Lourdes Almeida R, Freitas LM, Coqueiro-dos-Santos A, et al. Antigenic diversity of MASP gene family of Trypanosoma cruzi. Microbes and Infection. 2022 Sep;24(6–7):104982.
Valente M, Castillo-Acosta VM, Vidal AE, González-Pacanowska D. Overview of the role of kinetoplastid surface carbohydrates in infection and host cell invasion: prospects for therapeutic intervention. Parasitology. 2019 Dec;146(14):1743–54.
Clayton C. Regulation of gene expression in trypanosomatids: living with polycistronic transcription. Open Biol. 2019 Jun;9(6):190072.
Mayer MG, Floeter-Winter LM. Pre-mRNA trans-splicing: from kinetoplastids to mammals, an easy language for life diversity. Mem Inst Oswaldo Cruz. 2005 Aug;100(5):501–13.
Simpson L, Sbicego S, Aphasizhev R. Uridine insertion/deletion RNA editing in trypanosome mitochondria: A complex business. RNA. 2003 Mar;9(3):265–76.
Hajduk S, Ochsenreiter T. RNA editing in kinetoplastids. RNA Biology. 2010 Mar;7(2):229–36.
Hudu SA, Jimoh AO, Adeshina KA, Otalike EG, Tahir A, Hegazy AA. An insight into the Success, Challenges, and Future perspectives of eliminating Neglected tropical disease. Scientific African. 2024 Jun;24:e02165.
De Rycker M, Wyllie S, Horn D, Read KD, Gilbert IH. Anti-trypanosomatid drug discovery: progress and challenges. Nat Rev Microbiol. 2023 Jan;21(1):35–50.
Damasceno JD, Marques CA, Black J, Briggs E, McCulloch R. Read, Write, Adapt: Challenges and Opportunities during Kinetoplastid Genome Replication. Trends in Genetics. 2021 Jan;37(1):21–34.
Ewald S, Nasuhidehnavi A, Feng TY, Lesani M, McCall LI. The intersection of host in vivo metabolism and immune responses to infection with kinetoplastid and apicomplexan parasites. Lodoen MB, editor. Microbiol Mol Biol Rev. 2024 Mar 27;88(1):e00164-22.
Fairlamb AH, Wyllie S. The critical role of mode of action studies in kinetoplastid drug discovery. Front Drug Discov. 2023 May 10;3:1185679.
Rashidi S, Mansouri R, Ali-Hassanzadeh M, Muro A, Nguewa P, Manzano-Román R. The Defensive Interactions of Prominent Infectious Protozoan Parasites: The Host’s Complement System. Biomolecules. 2022 Oct 26;12(11):1564.
Shanmugasundram A, Starns D, Böhme U, Amos B, Wilkinson PA, Harb OS, et al. TriTrypDB: An integrated functional genomics resource for kinetoplastida. Reis-Cunha JL, editor. PLoS Negl Trop Dis. 2023 Jan 19;17(1):e0011058.
Rivara-Espasandín M, Palumbo MC, Sosa EJ, Radío S, Turjanski AG, Sotelo-Silveira J, et al. Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections. Front Pharmacol. 2023 Apr 6;14:1136321.
Van Den Kerkhof M, Sterckx Y, Leprohon P, Maes L, Caljon G. Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites. Microorganisms. 2020 Jun 24;8(6):950.
Kourbeli V, Chontzopoulou E, Moschovou K, Pavlos D, Mavromoustakos T, Papanastasiou IP. An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases. Molecules. 2021 Jul 30;26(15):4629.
Ware JM, O’Connell EM, Brown T, Wetzler L, Talaat KR, Nutman TB, et al. Efficacy and Tolerability of Miltefosine in the Treatment of Cutaneous Leishmaniasis. Clinical Infectious Diseases. 2021 Oct 5;73(7):e2457–562.
Milazzo G, Mercatelli D, Di Muzio G, Triboli L, De Rosa P, Perini G, et al. Histone Deacetylases (HDACs): Evolution, Specificity, Role in Transcriptional Complexes, and Pharmacological Actionability. Genes. 2020 May 15;11(5):556.
Wang Q, Rosa BA, Nare B, Powell K, Valente S, Rotili D, et al. Targeting Lysine Deacetylases (KDACs) in Parasites. Geary TG, editor. PLoS Negl Trop Dis. 2015 Sep 24;9(9):e0004026.
Soppa J. Protein Acetylation in Archaea, Bacteria, and Eukaryotes. Archaea. 2010;2010:1–9.
Zhong Q, Xiao X, Qiu Y, Xu Z, Chen C, Chong B, et al. Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications. MedComm. 2023 Jun;4(3):e261.
Gibbs DJ. Emerging Functions for N-Terminal Protein Acetylation in Plants. Trends in Plant Science. 2015 Oct;20(10):599–601.
Iyer A, Sidhu A, Subramaniam V. How important is the N-terminal acetylation of alpha-synuclein for its function and aggregation into amyloids? Front Neurosci. 2022 Nov 16;16:1003997.
Nguyen KT, Mun SH, Lee CS, Hwang CS. Control of protein degradation by N-terminal acetylation and the N-end rule pathway. Exp Mol Med. 2018 Jul;50(7):1–8.
Aksnes H, Hole K, Arnesen T. Molecular, Cellular, and Physiological Significance of N-Terminal Acetylation. In: International Review of Cell and Molecular Biology [Internet]. Elsevier; 2015 [cited 2024 Dec 15]. p. 267–305. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1937644815000027
Calis S, Gevaert K. The role of Nα‐terminal acetylation in protein conformation. The FEBS Journal. 2024 Jun 23;febs.17209.
Parks AR, Escalante-Semerena JC. Protein N-terminal acylation: An emerging field in bacterial cell physiology. CTMB. 2022 Dec 31;16:1–18.
Van Damme P, Osberg C, Jonckheere V, Glomnes N, Gevaert K, Arnesen T, et al. Expanded in vivo substrate profile of the yeast N-terminal acetyltransferase NatC. Journal of Biological Chemistry. 2023 Feb;299(2):102824.
Jiang N, Li W, Jiang S, Xie M, Liu R. Acetylation in pathogenesis: Revealing emerging mechanisms and therapeutic prospects. Biomedicine & Pharmacotherapy. 2023 Nov;167:115519.
Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, et al. Comparative Large Scale Characterization of Plant versus Mammal Proteins Reveals Similar and Idiosyncratic N-α-Acetylation Features. Molecular & Cellular Proteomics. 2012 Jun;11(6):M111.015131.
Avila CC, Mule SN, Rosa-Fernandes L, Viner R, Barisón MJ, Costa-Martins AG, et al. Proteome-Wide Analysis of Trypanosoma cruzi Exponential and Stationary Growth Phases Reveals a Subcellular Compartment-Specific Regulation. Genes. 2018 Aug 15;9(8):413.
Ochaya S, Respuela P, Simonsson M, Saraswathi A, Branche C, Lee J, et al. Characterization of a Trypanosoma cruzi acetyltransferase: cellular location, activity and structure☆. Molecular and Biochemical Parasitology. 2007 Apr;152(2):123–31.
Xia C, Tao Y, Li M, Che T, Qu J. Protein acetylation and deacetylation: An important regulatory modification in gene transcription (Review). Exp Ther Med [Internet]. 2020 Jul 29 [cited 2024 Dec 16]; Available from: http://www.spandidos-publications.com/10.3892/etm.2020.9073
Deng S, Marmorstein R. Protein N-Terminal Acetylation: Structural Basis, Mechanism, Versatility, and Regulation. Trends in Biochemical Sciences. 2021 Jan;46(1):15–27.
Abboud A, Bédoucha P, Byška J, Arnesen T, Reuter N. Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases. Computational and Structural Biotechnology Journal. 2020;18:532–47.
Dinh TV, Bienvenut WV, Linster E, Feldman‐Salit A, Jung VA, Meinnel T, et al. Molecular identification and functional characterization of the first Nα‐acetyltransferase in plastids by global acetylome profiling. Proteomics. 2015 Jul;15(14):2426–35.
Aksnes H, McTiernan N, Arnesen T. NATs at a glance. Journal of Cell Science. 2023 Jul 15;136(14):jcs260766.
Ametzazurra A, Gázquez C, Lasa M, Larrea E, Prieto J, Aldabe R. Characterization of the human Nα-terminal acetyltransferase B enzymatic complex. BMC Proc. 2009 Dec;3(S6):S4.
Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N, et al. Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc Natl Acad Sci USA. 2009 May 19;106(20):8157–62.
Morrison J, Altuwaijri NK, Brønstad K, Aksnes H, Alsaif HS, Evans A, et al. Missense NAA20 variantsimpairing the NatB protein N-terminal acetyltransferase cause autosomal recessivedevelopmental delay, intellectual disability, and microcephaly. Genetics in Medicine. 2021 Nov;23(11):2213–8.
Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, et al. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci USA. 2012 Jul 31;109(31):12449–54.
Starheim KK, Gromyko D, Evjenth R, Ryningen A, Varhaug JE, Lillehaug JR, et al. Knockdown of Human Nα -Terminal Acetyltransferase Complex C Leads to p53-Dependent Apoptosis and Aberrant Human Arl8b Localization. Molecular and Cellular Biology. 2009 Jul 1;29(13):3569–81.
Drazic A, Varland S. Human NAA30 can rescue yeast mak3∆ mutant growth phenotypes. Bioscience Reports. 2021 Mar 26;41(3):BSR20202828.
Hole K, Van Damme P, Dalva M, Aksnes H, Glomnes N, Varhaug JE, et al. The Human N-Alpha-Acetyltransferase 40 (hNaa40p/hNatD) Is Conserved from Yeast and N-Terminally Acetylates Histones H2A and H4. Imhof A, editor. PLoS ONE. 2011 Sep 15;6(9):e24713.
Song O kyu, Wang X, Waterborg JH, Sternglanz R. An N α-Acetyltransferase Responsible for Acetylation of the N-terminal Residues of Histones H4 and H2A. Journal of Biological Chemistry. 2003 Oct;278(40):38109–12.
Arnesen T, Marmorstein R, Dominguez R. Actin’s N‐terminal acetyltransferase uncovered. Cytoskeleton. 2018 Jul;75(7):318–22.
Varland S, Silva RD, Kjosås I, Faustino A, Bogaert A, Billmann M, et al. N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity. Nat Commun. 2023 Oct 27;14(1):6774.
Varland S, Silva RD, Kjosås I, Faustino A, Bogaert A, Billmann M, et al. N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity. Nat Commun. 2023 Oct 27;14(1):6774.
Liu Y, Feng W, Wang Y, Wu B. Crosstalk between protein post-translational modifications and phase separation. Cell Commun Signal. 2024 Feb 12;22(1):110.
Varland S, Osberg C, Arnesen T. N‐terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects. Proteomics. 2015 Jul;15(14):2385–401.
Schoijet AC, Sternlieb T, Alonso GD. Signal Transduction Pathways as Therapeutic Target for Chagas Disease. CMC. 2019 Dec 13;26(36):6572–89.
Raghul Kannan S, Tamizhselvi R. N-acetyltransferase and inflammation: Bridging an unexplored niche. Gene. 2023 Dec;887:147730.
Jiang Y, Jiang L, Akhil CS, Wang D, Zhang Z, Zhang W, et al. MULocDeep web service for protein localization prediction and visualization at subcellular and suborganellar levels. Nucleic Acids Research. 2023 Jul 5;51(W1):W343–9.
Giordani F, Morrison LJ, Rowan TG, De Koning HP, Barrett MP. The animal trypanosomiases and their chemotherapy: a review. Parasitology. 2016 Dec;143(14):1862–89.
Zhou X, Zheng W, Li Y, Pearce R, Zhang C, Bell EW, et al. I-TASSER-MTD: a deep-learning-based platform for multi-domain protein structure and function prediction. Nat Protoc. 2022 Oct;17(10):2326–53.
Abrusán G, Marsh JA. Alpha Helices Are More Robust to Mutations than Beta Strands. Orengo CA, editor. PLoS Comput Biol. 2016 Dec 9;12(12):e1005242.
Ribeiro AJM, Riziotis IG, Borkakoti N, Thornton JM. Enzyme function and evolution through the lens of bioinformatics. Biochemical Journal. 2023 Nov 29;480(22):1845–63.
Schilling B, Meyer JG, Wei L, Ott M, Verdin E. High-Resolution Mass Spectrometry to Identify and Quantify Acetylation Protein Targets. In: Brosh, RM, editor. Protein Acetylation [Internet]. New York, NY: Springer New York; 2019 [cited 2024 Dec 16]. p. 3–16. (Methods in Molecular Biology; vol. 1983). Available from: http://link.springer.com/10.1007/978-1-4939-9434-2_1
Neagu AN, Jayathirtha M, Baxter E, Donnelly M, Petre BA, Darie CC. Applications of Tandem Mass Spectrometry (MS/MS) in Protein Analysis for Biomedical Research. Molecules. 2022 Apr 8;27(8):2411.
Moloney NM, Barylyuk K, Tromer E, Crook OM, Breckels LM, Lilley KS, et al. Mapping diversity in African trypanosomes using high resolution spatial proteomics. Nat Commun. 2023 Jul 21;14(1):4401.
Sundar S, Singh B. Understanding Leishmania parasites through proteomics and implications for the clinic. Expert Review of Proteomics. 2018 May 4;15(5):371–90.
Ansori ANm, Antonius Y, Susilo RJk, Hayaza S, Kharisma VD, Parikesit AA, et al. Application of CRISPR-Cas9 genome editing technology in various fields: A review. Narra J. 2023 Aug 31;3(2):e184.
Laurent M, Geoffroy M, Pavani G, Guiraud S. CRISPR-Based Gene Therapies: From Preclinical to Clinical Treatments. Cells. 2024 May 8;13(10):800.
Carbajo CG, Han X, Savur B, Upadhyaya A, Taha F, Tinti M, et al. A high-throughput protein tagging toolkit that retains endogenous UTRs for studying gene regulation in Kinetoplastids [Internet]. Molecular Biology; 2024 [cited 2024 Dec 16]. Available from: http://biorxiv.org/lookup/doi/10.1101/2024.11.02.621556
Asencio C, Hervé P, Morand P, Oliveres Q, Morel CA, Prouzet‐Mauleon V, et al. Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker‐free gene editing in Trypanosoma and Leishmania. Molecular Microbiology. 2024 Jun;121(6):1079–94.
Foyn H, Thompson PR, Arnesen T. DTNB-Based Quantification of In Vitro Enzymatic N-Terminal Acetyltransferase Activity. In: Schilling O, editor. Protein Terminal Profiling [Internet]. New York, NY: Springer New York; 2017 [cited 2024 Dec 16]. p. 9–15. (Methods in Molecular Biology; vol. 1574). Available from: http://link.springer.com/10.1007/978-1-4939-6850-3_2
Asensio T, Dian C, Boyer JB, Rivière F, Meinnel T, Giglione C. A Continuous Assay Set to Screen and Characterize Novel Protein N-Acetyltransferases Unveils Rice General Control Non-repressible 5-Related N-Acetyltransferase2 Activity. Front Plant Sci. 2022 Feb 22;13:832144.
Woo H, Oh J, Cho YJ, Oh GT, Kim SY, Dan K, et al. N-terminal acetylation of Set1-COMPASS fine-tunes H3K4 methylation patterns. Sci Adv. 2024 Jul 12;10(28):eadl6280.
Kwon A, Lee GB, Park T, Lee JH, Ko P, You E, et al. Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer. Biomedicines. 2020 Sep 9;8(9):338.
Scott DC, Hammill JT, Min J, Rhee DY, Connelly M, Sviderskiy VO, et al. Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase. Nat Chem Biol. 2017 Aug 1;13(8):850–7.
Cupp-Sutton KA, Wu S. High-throughput quantitative top-down proteomics. Mol Omics. 2020;16(2):91–9.
Beneke T, Madden R, Makin L, Valli J, Sunter J, Gluenz E. A CRISPR Cas9 high-throughput genome editing toolkit for kinetoplastids. R Soc open sci. 2017 May;4(5):170095.