Abstract
Proteins containing WD40 domains play important roles in the formation of multiprotein complexes. Little is known about WD40 proteins in the malaria parasite. This report contains the initial description of a WD40 protein that is unique to the genus Plasmodium and possibly closely related genera. The N-terminal portion of this protein consists of seven WD40 repeats that are highly conserved in all Plasmodium species. Following the N-terminal region is a central region that is conserved within the major Plasmodium clades, such as parasites of great apes, monkeys, rodents, and birds, but partially conserved across all Plasmodium species. This central region contains extensive low-complexity sequence and is predicted to have a disordered structure. Proteins with disordered structure generally function in molecular interactions. The C-terminal region is semi-conserved across all Plasmodium species and has no notable features. This WD40 repeat protein likely functions in some aspect of parasite biology that is unique to Plasmodium and this uniqueness makes the protein a possible target for therapeutic intervention.
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Data has been deposited in databases where appropriate and the datasets and materials are available from the corresponding author on reasonable request.
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References
Aurrecoechea C, Brestelli J, Brunk BP et al (2009) PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res 37:539–543. https://doi.org/10.1093/nar/gkn814
Böhme U, Otto TD, Cotton JA et al (2018) Complete avian malaria parasite genomes reveal features associated with lineage-specific evolution in birds and mammals. Genome Res 28:547–560. https://doi.org/10.1101/gr.218123.116
Bunnik EM, Chung D-WD, Hamilton M et al (2013) Polysome profiling reveals translational control of gene expression in the human malaria parasite Plasmodium falciparum. Genome Biol 14:R128. https://doi.org/10.1186/gb-2013-14-11-r128
Chahar P, Kaushik M, Gill SS et al (2015) Genome-wide collation of the Plasmodium falciparum WDR protein superfamily reveals malarial parasite-specific features. PLoS ONE 10:e0128507. https://doi.org/10.1371/journal.pone.0128507
Chaudhry SR, Lwin N, Phelan D et al (2018) Comparative analysis of low complexity regions in Plasmodia. Sci Rep 8:335. https://doi.org/10.1038/s41598-017-18695-y
Chen F, Mackey AJ, Stoeckert CJJ, Roos DS (2006) OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups. Nucleic Acids Res 34:D363–D368. https://doi.org/10.1093/nar/gkj123
Cornejo O, Escalante AA (2006) The origin and age of Plasmodium vivax. Trends Parasitol 22:558–563. https://doi.org/10.1016/j.pt.2006.09.007
Cortés GT, Winograd E, Wiser MF (2003) Characterization of proteins localized to a subcellular compartment associated with an alternate secretory pathway of the malaria parasite. Mol Biochem Parasitol 129:127–135. https://doi.org/10.1016/S0166-6851(03)00097-5
Cortés GT, Wiser MF, Gómez-Alegría CJ (2020) Identification of Plasmodium falciparum HSP70-2 as a resident of the Plasmodium export compartment. Heliyon 6:e04037–e04037. https://doi.org/10.1016/j.heliyon.2020.e04037
DePristo MA, Zilversmit MM, Hartl DL (2006) On the abundance, amino acid composition, and evolutionary dynamics of low-complexity regions in proteins. Gene 378:19–30. https://doi.org/10.1016/j.gene.2006.03.023
Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6:197–208. https://doi.org/10.1038/nrm1589
Galen SC, Borner J, Martinsen ES et al (2018) The polyphyly of Plasmodium: comprehensive phylogenetic analyses of the malaria parasites (order Haemosporida) reveal widespread taxonomic conflict. R Soc Open Sci 5:171780. https://doi.org/10.1098/rsos.171780
Heintzelman MB, Mateer MJ (2008) GpMyoF, a WD40 repeat-containing myosin associated with the myonemes of Gregarina polymorpha. J Parasitol 94:158–168. https://doi.org/10.1645/GE-1339.1
Huang X, Miller W (1991) A time-efficient, linear-space local similarity algorithm. Adv Appl Math 12:337–357. https://doi.org/10.1016/0196-8858(91)90017-D
Jain BP, Pandey S (2018) WD40 repeat proteins: signalling scaffold with diverse functions. Protein J 37:391–406. https://doi.org/10.1007/s10930-018-9785-7
Kallio JP, Kursula I (2014) Recombinant production, purification and crystallization of the Toxoplasma gondii coronin WD40 domain. Acta Crystallogr Sect f, Struct Biol Commun 70:517–521. https://doi.org/10.1107/S2053230X14005196
Kelley LA, Mezulis S, Yates CM et al (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10:845–858. https://doi.org/10.1038/nprot.2015.053
Klausen MS, Anderson MV, Jespersen MC et al (2015) LYRA, a webserver for lymphocyte receptor structural modeling. Nucleic Acids Res 43:W349–W355. https://doi.org/10.1093/nar/gkv535
Krawczyk K, Liu X, Baker T et al (2014) Improving B-cell epitope prediction and its application to global antibody-antigen docking. Bioinformatics 30:2288–2294. https://doi.org/10.1093/bioinformatics/btu190
LaCount DJ, Vignali M, Chettier R et al (2005) A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438:103–107. https://doi.org/10.1038/nature04104
Lapp SA, Mok S, Zhu L et al (2015) Plasmodium knowlesi gene expression differs in ex vivo compared to in vitro blood-stage cultures. Malar J 14:110. https://doi.org/10.1186/s12936-015-0612-8
Larkin MA, Blackshields G, Brown NP et al (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23:2947–2948. https://doi.org/10.1093/bioinformatics/btm404
Llinás M, Bozdech Z, Wong ED et al (2006) Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains. Nucleic Acids Res 34:1166–1173. https://doi.org/10.1093/nar/gkj517
López-Barragán MJ, Lemieux J, Quiñones M et al (2011) Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum. BMC Genomics 12:1–13. https://doi.org/10.1186/1471-2164-12-587
Loy DE, Liu W, Li Y et al (2017) Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. Int J Parasitol 47:87–97. https://doi.org/10.1016/j.ijpara.2016.05.008
Ma J, An K, Zhou J-B et al (2019) WDSPdb: an updated resource for WD40 proteins. Bioinformatics 35:4824–4826. https://doi.org/10.1093/bioinformatics/btz460
Marchler-Bauer A, Bo Y, Han L et al (2017) CDD/SPARCLE: functional classification of proteins via subfamily domain architectures. Nucleic Acids Res 45:D200–D203. https://doi.org/10.1093/nar/gkw1129
Martinsen ES, Perkins SL, Schall JJ (2008) A three-genome phylogeny of malaria parasites (Plasmodium and closely related genera): evolution of life-history traits and host switches. Mol Phylogenet Evol 47:261–273. https://doi.org/10.1016/j.ympev.2007.11.012
Otto TD, Böhme U, Jackson AP et al (2014) A comprehensive evaluation of rodent malaria parasite genomes and gene expression. BMC Biol 12:86. https://doi.org/10.1186/s12915-014-0086-0
Pelle KG, Oh K, Buchholz K et al (2015) Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection. Genome Med 7:19. https://doi.org/10.1186/s13073-015-0133-7
Ramiro RS, Reece SE, Obbard DJ (2012) Molecular evolution and phylogenetics of rodent malaria parasites. BMC Evol Biol 12:219. https://doi.org/10.1186/1471-2148-12-219
Rawlings ND, Barrett AJ (1995) Evolutionary families of metallopeptidases. Methods Enzymol 248:183–228. https://doi.org/10.1016/0076-6879(95)48015-3
Reynolds CR, Islam SA, Sternberg MJE (2018) EzMol: a web server wizard for the rapid visualization and image production of protein and nucleic acid structures. J Mol Biol 430:2244–2248. https://doi.org/10.1016/j.jmb.2018.01.013
Rovira-Graells N, Gupta AP, Planet E et al (2012) Transcriptional variation in the malaria parasite Plasmodium falciparum. Genome Res 22:925–938. https://doi.org/10.1101/gr.129692.111
Short JM, Fernandez JM, Sorge JA, Huse WD (1988) Lambda ZAP: a bacteriophage lambda expression vector with in vivo excision properties. Nucleic Acids Res 16:7583–7600. https://doi.org/10.1093/nar/16.15.7583
Sigrist CJA, De Castro E, Cerutti L et al (2013) New and continuing developments at PROSITE. Nucleic Acids Res 41:D344–D347. https://doi.org/10.1093/nar/gks1067
Silva JC, Egan A, Arze C et al (2015) A new method for estimating species age supports the coexistence of malaria parasites and their mammalian hosts. Mol Biol Evol 32:1354–1364. https://doi.org/10.1093/molbev/msv005
Song R, Wang Z-D, Schapira M (2017) Disease association and druggability of WD40 repeat proteins. J Proteome Res 16:3766–3773. https://doi.org/10.1021/acs.jproteome.7b00451
Sonnhammer EL, Von Heijne G, Krogh A (1998) A hidden Markov model for predicting transmembrane helices in protein sequences. Proc Int Conf Intell Syst Mol Biol 6:175–182
Stirnimann C, Petsalaki E, Russell R, Müller C (2010) WD40 proteins cellular networks. Trends Biochem Sci 35:565–574. https://doi.org/10.1016/j.tibs.2010.04.003
Sundararaman SA, Plenderleith LJ, Liu W et al (2016) Genomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria. Nat Commun 7:11078. https://doi.org/10.1038/ncomms11078
Tachibana SI, Sullivan SA, Kawai S et al (2012) Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade. Nat Genet 44:1051–1055. https://doi.org/10.1038/ng.2375
Tompa P (2003) Intrinsically unstructured proteins evolve by repeat expansion. BioEssays 25:847–855. https://doi.org/10.1002/bies.10324
von Bohl A, Kuehn A, Simon N et al (2015) A WD40-repeat protein unique to malaria parasites associates with adhesion protein complexes and is crucial for blood stage progeny. Malar J 14:435. https://doi.org/10.1186/s12936-015-0967-x
Wang Y, Jiang F, Zhuo Z et al (2013) A method for WD40 repeat detection and secondary structure prediction. PLoS ONE 8:e65705. https://doi.org/10.1371/journal.pone.0065705
Waterhouse A, Bertoni M, Bienert S et al (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46:W296–W303. https://doi.org/10.1093/nar/gky427
Wiser MF (2007) Export and trafficking of Plasmodium proteins within the host erythrocyte. Acta Biológica Colomb 12:3–18
Wootton JC (1994) Non-globular domains in protein sequences: automated segmentation using complexity measures. Comput Chem 18:269–285. https://doi.org/10.1016/0097-8485(94)85023-2
Xu D, Zhang Y (2012) Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field. Proteins 80:1715–1735. https://doi.org/10.1002/prot.24065
Yang Y, Faraggi E, Zhao H, Zhou Y (2011) Improving protein fold recognition and template-based modeling by employing probabilistic-based matching between predicted one-dimensional structural properties of query and corresponding native properties of templates. Bioinformatics 27:2076–2082. https://doi.org/10.1093/bioinformatics/btr350
Zanghì G, Vembar SS, Baumgarten S et al (2018) A specific PfEMP1 is expressed in P. falciparum sporozoites and plays a role in hepatocyte infection. Cell Rep 22:2951–2963. https://doi.org/10.1016/j.celrep.2018.02.075
Zhang K, Fujioka H, Lobo CA et al (1999) Cloning and characterization of a new asparagine-rich protein in Plasmodium falciparum. Parasitol Res 85:956–963. https://doi.org/10.1007/s004360050666
Zhang M, Wang C, Otto TD et al (2018) Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science 360:eaap7847. https://doi.org/10.1126/science.aap7847
Zhu L, Mok S, Imwong M et al (2016) New insights into the Plasmodium vivax transcriptome using RNA-Seq. Sci Rep 6:20498. https://doi.org/10.1038/srep20498
Acknowledgements
Acknowledgments to the Instituto Nacional de Salud, Bogotá, D.C., Colombia, where the original work was initiated.
Funding
This work was supported by the Universidad Nacional de Colombia, Vicerrectoria de Investigación y extensión (Strategic Research Project-Hermes 42917), Medicine Faculty (Public Health Department and Laboratorio de equipos comunes), Programa de doctorado del Instituto de Biotecnología, Departamento de Farmacia, Facultad de Ciencias and Doctorado en Medicina Tropical, Universidad de Cartagena- SUE-Caribe. This project was also funded in part by a grant from the Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (Colciencias-project no. 110140820398).
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Cortés, Gladys T.: Investigation, Methodology (gene cloning), Writing — Review & Editing, Conceptualization, Resources, Funding acquisition. Gonzalez Beltran, Martha Margarita: Methodology (molecular modeling). Gómez-Alegría, Claudio J.: Writing — Review & Editing, Conceptualization, Resources, Supervision. Wiser, Mark F.: Writing — Original Draft, Visualization, Formal analysis (in silico), Methodology (molecular modeling), Conceptualization, Supervision.
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Highlights
• Few proteins containing WD40 domains from the malaria parasite have been characterized
• PlasWD40-1 is a WD40 domain-containing protein only found in Plasmodium species
• The WD40 domain of PlasWD40-1 is highly conserved across all Plasmodium species
• A large portion of PlasWD40-1 is composed of low-complexity sequence
• PlasWD40-1 likely plays a role related to the unique biology of Plasmodium
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Cortés, G.T., Beltran, M.M.G., Gómez-Alegría, C.J. et al. Identification of a protein unique to the genus Plasmodium that contains a WD40 repeat domain and extensive low-complexity sequence. Parasitol Res 120, 2617–2629 (2021). https://doi.org/10.1007/s00436-021-07190-z
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DOI: https://doi.org/10.1007/s00436-021-07190-z