Apicortin and Its Tentative Role: Comparison
View Latest Version
Please note this is a comparison between Version 1 by Ferenc Orosz and Version 4 by Ferenc Orosz.

Apicortin was identified in silico, in 2009, as a characteristic protein of apicomplexans. It combines a partial p25alpha domain with a DCX (doublecortin) one. Based on its occurrence and one of its characteristic domains, it was termed apicortin. Apicortin, when identified, was shown to occur in apicomplexan parasites and in the placozoan animal, Trichoplax adhaerens. The apicomplexan genomes known then contained it without exception. This situation practically has not changed since then; this statement is valid for the newly sequenced genomes and transcriptomes of apicomplexans as well, almost without exception.

  • apicortin
  • Plasmodium
  • Toxoplasma
  • p25alpha domain
  • DCX domain
  • apicomplexa
  • conoid

[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]1. Overview

In 2009, apicortin was identified in silico as a characteristic protein of apicomplexans that also occurs in the placozoa, Trichoplax adhaerens. Since then, it has been found that apicortin also occurs in free-living cousins of apicomplexans (chromerids) and in flagellated fungi. It contains a partial p25-α domain and a doublecortin (DCX) domain, both of which have tubulin/microtubule binding properties. Apicortin has been studied experimentally in two very important apicomplexan pathogens, Toxoplasma gondii and Plasmodium falciparum. It is localized in the apical complex in both parasites. In T. gondii, apicortin plays a key role in shaping the structure of a special tubulin polymer, conoid. In both parasites, its absence or downregulation has been shown to impair pathogen–host interactions. Based on these facts, it has been suggested as a therapeutic target for treatment of malaria and toxoplasmosis.

2. Description2. Name

2.1. Name

Apicortin was identified in silico, in 2009, as a characteristic protein of apicomplexans[1] [1]. It combines a partial p25alpha domain with a DCX (doublecortin) one. Based on its occurrence and one of its characteristic domains, it was termed apicortin. In T. gondii it is also known as TgDCX [2].

2.2. History and occurrence

3. Apicortin

Apicortin, when identified, was shown to occur in apicomplexan parasites and in the placozoan animal, Trichoplax adhaerens[1] [1]. The apicomplexan genomes known then contained it without exception. This situation practically has not changed since then; this statement is valid for the newly sequenced genomes and transcriptomes of apicomplexans as well. The only exception is the Apicomplexa with the smallest genome, Babesia microti[3] [2].
Later it has been found that apicortin also occurs in chromerids[4], the recently discovered[5][6] [3,4], free-living cousins of apicomplexans [5]. This is not surprising, given the phylogenetic proximity and the structural similarity of these phyla. Unlike apicomplexan species, both Chromera velia and Vitrella brassicaformis have three apicortin paralogs. Apicortin has not been found in other related phyla of the Alveolata superphylum, although its remnant is present in the genome in the case of Perkinsozoa[7] [6]. However, the very recently published draft genome of Perkinsus olseni contains hypothetical protein(s) possessing both p25alpha and DCX domains (KAF4710163, KAF4750811)[8] [7].
It has also been revealed that some primitive fungi also possess this protein; first it was shown in the cases of Spizellomyces punctatus[7] [6] and Rozella allomycis[4] [5]. Later, a systematic examination of fungal genomes showed that the flagellated fungi contain apicortin almost without exception; and it is present even in a non-flagellated but also deeper branching clade (phylum Mucoromycota, class Endogonomycetes)[9] [8].
Apicortin is one of the most abundant proteins of T. adhaerens[10] [9]. This is the only animal that possesses apicortin[11] [10]. Animal draft genomes and transcriptomes contain sometimes nucleotide sequences, contigs and TSAs (transcriptome shot-gun assemblies), homologous to apicortin, but they have been shown to be contaminations from parasitizing apicomplexans, based on sequence similarities and GC ratios[12][13] [11,12]. In the case of T. adhaerens, this option was excluded by phylogenetic analysis [8].  Several authors suggested that the presence of frequent contaminants could serve as a basis for the identification of hitherto unknown apicomplexans and, in general, parasites [13,14,15]. The origin of a few plant and algal apicortin-like nucleotide sequences needs further investigations.  My preliminary data suggest that contamination of apicomplexan origin can be ruled out but not that of fungal ones.
Strong correlation between the presence of the p25alpha domain and that of the eukaryotic flagellum was suggested before the identification of apicortin[14] [16]. With very few exceptions, each flagellated organism contains p25alpha domain-containing proteins; on the other side, in non-flagellated species, the p25alpha domain generally does not occur[11] [8,10]. The protein that contains the p25alpha domain varies depending on the phylum; e.g., it is the so called “long-type” TPPP in animals (except T. adhaerens)[11][15] [10,17], a fungal-type TPPP and apicortin in flagellated fungi [8], while the “short-type” TPPP and apicortin are found in apicomplexan species[11] [10]. With the exceptions of two non-flagellated fungi and some apicomplexans, apicortin can be found only in species which are flagellated, at least in some life stage.

2.3. Domains

4. Domains

Apicortin belongs to a eukaryotic protein superfamily, the TPPP-like proteins, characterized by the presence of the p25alpha domain (Pfam05517, IPR008907), and named after the first identified member, TPPP/p25, which exhibits microtubule stabilizing function[11] [10]. TPPP stands for tubulin polymerization promoting protein[16][17] [18,19] and was first identified by Takahashi et al. as p25 protein[18] [20]. Full-length p25alpha domain consists of about 160 amino acids; however, that of the apicortin is incomplete, containing only the last 30–40 amino acids (a “partial p25alpha domain”). Importantly, the tubulin/microtubule binding amino acid sequence is located in this part of the domain[19][20][21][22] [21,22,23,24]. This is the most conserved part of the domain, which contains a characteristic “Rossmann-like motif”, GXGXGXXGR[11][15] [10,17]. However, apicortins possess another characteristic domain, the DCX one (Pfam03607, IPR003533)[1] [1]. The DCX (doublecortin) domain is named after the brain-specific X-linked gene doublecortin[23] [25]. It is a structural domain, which generally appears in duplicate as two tandemly repeated 80 amino acid regions (N- and C-terminal type DCX domains), but proteins containing only one DCX-repeat have also been identified[24][25] [26,27]. This domain is also known to play a role in the stabilization of microtubules[23][24] [25,26]. 

2.4. Structure

Apicortins consist of four structural units: (i) a long, disordered N-terminal domain; (ii) a partial p25alpha domain; (iii) a disordered linker region; (iv) and a DCX domain[7].

The N-terminal part consists of about 70–90 amino acids in apicomplexan apicortins, similarly to the apicortins of the few non-flagellated fungi; this part is 40 amino acid long in one of the C. velia apicortins (Cvel_6797) while in other species (placozoa, chromerids, flagellated fungi) it is absent. The N-terminus of the proteins is rather different among the various apicomplexan species. It is not conserved among the species belonging to different classes of Apicomplexa, or the various genera of the same class, or even among the various Plasmodium subgenera. The extra N-terminal regions are significantly similar in the two fungal apicortins possessing it. Concerning the secondary structure, the N-terminal region of apicortins was shown to be highly disordered by predictor programs based on different principles[4][7][9].

The partial p25alpha domain, in general, is the most conservative part of the protein, however, there are two exceptions. R. allomycis and Plasmodium orthologs present in species infecting mammals (but not birds) lack the final part of this domain, which includes the Rossmann-like motif. Otherwise, the sequences are very similar, independently of whether the protein can be found in an apicomplexan species or not. It was shown by Leung et al.[2] that this region of the protein has an outstanding role in tubulin binding.

In the linker (interdomain) region, which has also been predicted to be unstructured, similarity is much lower between protist and non-protist apicortins. Moreover, this part of Plasmodium proteins also differs somewhat from those of the other apicomplexan orthologs.

In the DCX domain, the overall similarity is somewhat lower between the two groups than in the case of the partial p25alpha domain; however, there is no exception: the similarity occurs through the whole domain in all orthologs. Phylogenetic analysis showed that DCX domains of apicortins are clustered neither with C- nor N-terminal type domains but form a separate group[4].

2.5. Phylogenetics

Phylogenetic analysis clearly showed that apicomplexan apicortins form a monophyletic group and are well separated from opisthokont (fungal and placozoan) and chromerid apicortins[4][9]. One pair of the chromerid apicortins is a sister group to them, the other 2-2 chromerid homologs are significantly different.

2.6. Apicomplexan apicortins

Apicortin is a characteristic protein of Apicomplexa. It is present in both classes, Aconoidasida and Conoidasida, and in each order and family whose species are fully sequenced. According to the NCBI website, 66 genomes of apicomplexan species have been fully sequenced, 65 of which contain apicortin. The only exception, B. microti has a significantly decreased genome which is the smallest one in the phylum[3]. However, it contains a p25alpha domain containing protein, a short-type TPPP (XP_012649535).

The genomes of most Plasmodium species have been sequenced (21), due to their epidemiological significance, followed by 15 sequenced Cryptosporidium species genomes. Apicomplexans are obligate parasites causing serious illnesses in humans and domestic animals[26]. Species in the genus Plasmodium cause malaria, from which over 200 million people suffer each year. The official deaths according to WHO were about 400,000 both in 2018 and 2019[27]. Other members of the phylum Apicomplexa are responsible for animal sicknesses, such as coccidiosis and babesiosis, resulting in significant economic burden for animal husbandry. Cryptosporidium causes cryptosporidiosis in humans and animals, Theileria causes tropical theileriosis and East Coast fever in cattle, and Toxoplasma causes toxoplasmosis in immunocompromised patients and congenitally infected fetuses. The disease-causing parasites belong to the orders Haemosporida, Piroplasmida and Eucoccidiorida, which explains the bias in genome sequencing.

2.7. Function in apicomplexans

Apicomplexans are an ancient and diverse phylum with peculiar cell biological properties. Many of the distinct traits are related to the unique cytoskeletal elements of these parasites[28]. In addition to microtubules, the main cytoskeletal constituents, several apicomplexans possess another polymer form of tubulin, the conoid[29]  that has an important role in host cell invasion. The conoid fibers resemble microtubules but their subunits are curled into an extremely tight coil, where tubulin is arranged into a polymer form that is different from typical microtubules[30]. In T. gondii, apicortin is only localized at the conoid as shown by immunofluorescence staining and the labeling suggested that it is distributed all along the conoid fibers[2][31]; moreover, apicortin is essential for providing the correct structure and function of conoid[2]. In P. falciparum, which has no conoid, apicortin was observed at the apical end of the parasite suggesting its role in apical complex formation. It was co-localized with both α- and β-tubulin[32][33]. In both species, downregulation of apicortin leads to impaired host cell invasion[2][33]. Moreover, apicortin knockout T. gondii grew about four times slower compared with the wild-type ones[31].

35. Conclusions and Prospects

When apicortin was identified in silico, it was proposed that its function may be to stabilize specific cytoskeletal structures that are unique to apicomplexans[1] [1]. It has also been hypothesized that it might have a role in parasite–host interactions[1][7] [1,5]. Recent experimental results support both assumptions[2][31][32][33][34] [28,29,30,31]. Apicortin has been shown to be localized in the apical complex; more precisely, in T. gondii, it is localized exclusively at the conoid, a tubulin-based structure that has an important role in host cell invasion [29]. Apicortin is essential for providing the correct structure and function of conoid. In P. falciparum, which has no conoid, apicortin is localized at the apical end; it has been suggested that it is involved in the formation of the apical complex [30]. In both species, downregulation of apicortin leads to impaired host cell invasion [28,31]. Apicomplexan species possess several hundred genes, which are specific for the phylum, and even more genes, which are absent in mammals/vertebrates but are present in these parasites. For example, apicomplexans have evolved hundreds of specialized invasion proteins, and contain lineage- and species-specific gene families, which are specialized for modulating host-specific adaptation[35] [32]. Targeting parasite proteins that have crucial roles in these interactions is a key focus in the development of therapeutic agents against diseases caused by apicomplexan infection. Thus, apicortin, which seems to influence parasite–host interactions, is also a potential drug target. Since some mechanistic details of its function have been known, this protein has become more than a desirable target in drug development. However, the role of apicortin in phyla other than Apicomplexa has remained enigmatic.

References

  1. Orosz, F. Apicortin, a unique protein, with a putative cytoskeletal role, shared only by apicomplexan parasites and the plac-ozoan Trichoplax adhaerens. Infect. Genet. Evol. 2009, 9, 1275–1286, doi:10.1016/j.meegid.2009.09.001.
  2. Eiji Nagayasu; Yu-Chen Hwang; Jun Liu; John M. Murray; Ke Hu; Loss of a doublecortin (DCX)-domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion. Molecular Biology of the Cell 2017, 28, 411-428, 10.1091/mbc.e16-08-0587.Cornillot, E.; Hadj-Kaddour, K.; Dassouli, A.; Noel, B.; Ranwez, V.; Vacherie, B.; Augagneur, Y.; Brès, V.; Duclos, A.; Randazzo, S.; et al. Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti. Nucleic Acids Res. 2012, 40, 9102–9114, doi:10.1093/nar/gks700.
  3. Emmanuel Cornillot; Kamel Hadj-Kaddour; Amina Dassouli; Benjamin Noel; Vincent Ranwez; Benoît Vacherie; Yoann Augagneur; Virginie Bres; Antoine Duclos; Sylvie Randazzo; et al.Bernard CarcyFrançoise Debierre-GrockiegoStéphane DelbecqKarina Moubri-MénageHosam Shams-EldinSahar Usmani-BrownFrédéric BringaudPatrick WinckerChristian P. VivarèsRalph T. SchwarzTheo P. SchettersPeter J. KrauseAndré GorenflotVincent BerryValérie BarbeChoukri Ben Mamoun Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti†. Nucleic Acids Research 2012, 40, 9102-9114, 10.1093/nar/gks700.Moore, R.B.; Oborník, M.; Janouškovec, J.; Chrudimský, T.; Vancová, M.; Green, D.H.; Wright, S.W.; Davies, N.W.; Bolch, C.J.; Heimann, K.; et al. A photosynthetic alveolate closely related to apicomplexan parasites. Nature 2008, 451, 959–963, doi:10.1038/nature06635.
  4. Ferenc Orosz; Wider than Thought Phylogenetic Occurrence of Apicortin, A Characteristic Protein of Apicomplexan Parasites. Journal of Molecular Evolution 2016, 82, 303-314, 10.1007/s00239-016-9749-5.Oborník, M.; Modrý, D.; Lukeš, M.; Cernotíková-Stříbrná, E.; Cihlář, J.; Tesařová, M.; Kotabová, E.; Vancová, M.; Prášil, O.; Lukeš, J. Morphology ultrastructure and life cycle of Vitrella brassicaformis n. sp., n. gen., a novel chromerid from the Great Barrier Reef. Protist 2012, 163, 306–323, doi:10.1016/j.protis.2011.09.001.
  5. Moore, R.B.; Oborník, M.; Janouškovec, J.; Chrudimský, T.; Vancová, M.; Green, D.H.; Wright, S.W.; Davies, N.W.; Bolch, C.J.; Heimann, K.; et al. A photosynthetic alveolate closely related to apicomplexan parasites. Nature 2008, 451, 959–963, doi:10.1038/nature06635.Orosz, F. Apicomplexan apicortins possess a long disordered N-terminal extension. Infect. Genet. Evol. 2011, 11, 1037–1044, doi:10.1016/j.meegid.2011.03.023.
  6. Oborník, M.; Modrý, D.; Lukeš, M.; Cernotíková-Stříbrná, E.; Cihlář, J.; Tesařová, M.; Kotabová, E.; Vancová, M.; Prášil, O.; Lukeš, J. Morphology ultrastructure and life cycle of Vitrella brassicaformis n. sp., n. gen., a novel chromerid from the Great Barrier Reef. Protist 2012, 163, 306–323, doi:10.1016/j.protis.2011.09.001.Bogema, D.R.; Yam, J.; Micallef, M.L.; Gholipourkanani, H.; Go, J.; Jenkins, C.; Dang, C. Draft genomes of Perkinsus olseni and Perkinsus chesapeaki reveal polyploidy and regional differences in heterozygosity. Genomics 2021, 113, 677–688, doi:10.1016/j.ygeno.2020.09.064.
  7. Ferenc Orosz; Apicomplexan apicortins possess a long disordered N-terminal extension. Infection, Genetics and Evolution 2011, 11, 1037-1044, 10.1016/j.meegid.2011.03.023.Orosz, F. Wider than thought phylogenetic occurrence of apicortin, a characteristic protein of apicomplexan parasites. J. Mol. Evol. 2016, 82, 303–314, doi:10.1007/s00239-016-9749-5.
  8. Orosz, F. Wider than thought phylogenetic occurrence of apicortin, a characteristic protein of apicomplexan parasites. J. Mol. Evol. 2016, 82, 303–314, doi:10.1007/s00239-016-9749-5.Orosz, F. On the TPPP-like proteins of flagellated fungi. Fungal Biol. 2021, 125, 357–367, doi:10.1016/j.funbio.2020.12.001.
  9. Ferenc Orosz; On the TPPP-like proteins of flagellated fungi. Fungal Biology 2020, 125, 357-367, 10.1016/j.funbio.2020.12.001.Ringrose, J.H.; van den Toorn, H.W.P.; Eitel, M.; Post, H.; Neerincx, P.; Schierwater, B.; Altelaar, A.F.M.; Heck, A.J.R. Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity. Nat. Commun. 2013, 4, 1408, doi:10.1038/ncomms2424.
  10. Ringrose, J.H.; van den Toorn, H.W.P.; Eitel, M.; Post, H.; Neerincx, P.; Schierwater, B.; Altelaar, A.F.M.; Heck, A.J.R. Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity. Nat. Commun. 2013, 4, 1408, doi:10.1038/ncomms2424.Orosz, F. A new protein superfamily: TPPP-like proteins. PLoS ONE 2012, 7, e49276, doi:10.1371/journal.pone.0049276.
  11. Orosz, F. A new protein superfamily: TPPP-like proteins. PLoS ONE 2012, 7, e49276, doi:10.1371/journal.pone.0049276.Orosz, F. Two recently sequenced vertebrate genomes are contaminated with apicomplexan species of the Sarcocystidae family. Int. J. Parasitol. 2015, 45, 871–878, doi:10.1016/j.ijpara.2015.07.002.
  12. Orosz, F. Two recently sequenced vertebrate genomes are contaminated with apicomplexan species of the Sarcocystidae family. Int. J. Parasitol. 2015, 45, 871–878, doi:10.1016/j.ijpara.2015.07.002.Orosz, F. Does apicortin, a characteristic protein of apicomplexan parasites and placozoa, occur in Eumetazoa? Acta Parasitol. 2018, 63, 617–633, doi:10.1515/ap-2018-0071.
  13. Orosz, F. Does apicortin, a characteristic protein of apicomplexan parasites and placozoa, occur in Eumetazoa? Acta Parasitol. 2018, 63, 617–633, doi:10.1515/ap-2018-0071.Borner, J.; Burmester, T. Parasite infection of public databases: A data mining approach to identify apicomplexan contamina-tions in animal genome and transcriptome assemblies. BMC Genomics 2017, 18, 100, doi:10.1186/s12864-017-3504-1.
  14. Orosz, F.; Ovádi, J. TPPP orthologs are ciliary proteins. FEBS Lett. 2008, 582, 3757–3764, doi:10.1016/j.febslet.2008.10.011.Lopes, R.J.; Mérida, A.M.; Carneiro, M. Unleashing the potential of public genomic resources to find parasite genetic data. Trends Parasitol. 2017, 33, 750–753, doi:10.1016/j.pt.2017.06.006.
  15. Vincze, O.; Tőkési, N.; Oláh, J.; Hlavanda, E.; Zotter, Á.; Horváth, I.; Lehotzky, A.; Tirián, L.; Medzihradszky, K.F.; Kovács, J.; et al. Tubulin polymerization promoting proteins (TPPPs): Members of a new family with distinct structures and functions. Biochemistry 2006, 45, 13818–13826, doi:10.1021/bi061305e.Orosz, F. On the benefit of publishing uncurated genome assembly data. J. Bacteriol. Parasitol. 2017, 8, 317, doi:10.4172/2155-9597.1000317.
  16. Hlavanda, E.; Kovács, J.; Oláh, J.; Orosz, F.; Medzihradszky, K.F.; Ovádi, J. Brain-specific p25 protein binds to tubulin and microtubules and induces aberrant microtubule assemblies at substoichiometric concentrations. Biochemistry 2002, 41, 8657–8664, doi:10.1021/bi020140g.Orosz, F.; Ovádi, J. TPPP orthologs are ciliary proteins. FEBS Lett. 2008, 582, 3757–3764, doi:10.1016/j.febslet.2008.10.011.
  17. Tirián, L.; Hlavanda, E.; Oláh, J.; Horváth, I.; Orosz, F.; Szabó, B.; Kovács, J.; Szabad, J.; Ovádi, J. TPPP/p25 promotes tubulin assemblies and blocks mitotic spindle formation. Proc. Natl. Acad. Sci. USA 2003, 100, 13976–13981, doi:10.1073/pnas.2436331100.Vincze, O.; Tőkési, N.; Oláh, J.; Hlavanda, E.; Zotter, Á.; Horváth, I.; Lehotzky, A.; Tirián, L.; Medzihradszky, K.F.; Kovács, J.; et al. Tubulin polymerization promoting proteins (TPPPs): Members of a new family with distinct structures and functions. Biochemistry 2006, 45, 13818–13826, doi:10.1021/bi061305e.
  18. Takahashi, M.; Tomizawa, K.; Ishiguro, K.; Sato, K.; Omori, A.; Sato, S.; Shiratsuchi, A.; Uchida, T.; Imahori, K. A novel brainspecific 25 kDa protein (p25) is phosphorylated by a Ser/Thr-Pro kinase (TPK II) from tau protein kinase fractions. FEBS Lett. 1991, 289, 37–43, doi:10.1016/0014-5793(91)80903-g.Hlavanda, E.; Kovács, J.; Oláh, J.; Orosz, F.; Medzihradszky, K.F.; Ovádi, J. Brain-specific p25 protein binds to tubulin and microtubules and induces aberrant microtubule assemblies at substoichiometric concentrations. Biochemistry 2002, 41, 8657–8664, doi:10.1021/bi020140g.
  19. Hlavanda, E.; Klement, E.; Kókai, E.; Kovács, J.; Vincze, O.; Tőkési, N.; Orosz, F.; Medzihradszky, K.F.; Dombrádi, V.; Ovádi, J. Phosphorylation blocks the activity of tubulin polymerization-promoting protein TPPP: Identification of sites targeted by dif-ferent kinases. J. Biol. Chem. 2007, 282, 29531–29539, doi:10.1074/jbc.M703466200.Tirián, L.; Hlavanda, E.; Oláh, J.; Horváth, I.; Orosz, F.; Szabó, B.; Kovács, J.; Szabad, J.; Ovádi, J. TPPP/p25 promotes tubulin assemblies and blocks mitotic spindle formation. Proc. Natl. Acad. Sci. USA 2003, 100, 13976–13981, doi:10.1073/pnas.2436331100.
  20. Tőkési, N.; Oláh, J.; Hlavanda, E.; Szunyogh, S.; Szabó, A.; Babos, F.; Magyar, A.; Lehotzky, A.; Vass, E.; Ovádi, J. Identification of motives mediating alternative functions of the neomorphic moonlighting TPPP/p25. Biochim. Biophys. Acta 2014, 1842, 547–557, doi:10.1016/j.bbadis.2014.01.009.Takahashi, M.; Tomizawa, K.; Ishiguro, K.; Sato, K.; Omori, A.; Sato, S.; Shiratsuchi, A.; Uchida, T.; Imahori, K. A novel brainspecific 25 kDa protein (p25) is phosphorylated by a Ser/Thr-Pro kinase (TPK II) from tau protein kinase fractions. FEBS Lett. 1991, 289, 37–43, doi:10.1016/0014-5793(91)80903-g.
  21. DeBonis, S.; Neumann, E.; Skoufias, D. Self protein-protein interactions are involved in TPPP/p25 mediated microtubule bundling. Sci. Rep. 2015, 5, 13242, doi:10.1038/srep13242.Hlavanda, E.; Klement, E.; Kókai, E.; Kovács, J.; Vincze, O.; Tőkési, N.; Orosz, F.; Medzihradszky, K.F.; Dombrádi, V.; Ovádi, J. Phosphorylation blocks the activity of tubulin polymerization-promoting protein TPPP: Identification of sites targeted by dif-ferent kinases. J. Biol. Chem. 2007, 282, 29531–29539, doi:10.1074/jbc.M703466200.
  22. Oláh, J.; Szénási, T.; Szabó, A.; Kovács, K.; Lőw, P.; Štifanić, M.; Orosz, F. Tubulin binding and polymerization promoting properties of TPPP proteins are evolutionarily conserved. Biochemistry 2017, 56, 1017–1024, doi:10.1021/acs.biochem.6b00902.Tőkési, N.; Oláh, J.; Hlavanda, E.; Szunyogh, S.; Szabó, A.; Babos, F.; Magyar, A.; Lehotzky, A.; Vass, E.; Ovádi, J. Identification of motives mediating alternative functions of the neomorphic moonlighting TPPP/p25. Biochim. Biophys. Acta 2014, 1842, 547–557, doi:10.1016/j.bbadis.2014.01.009.
  23. Sapir, T.; Horesh, D.; Caspi, M.; Atlas, R.; Burgess, H.A. Doublecortin mutations cluster in evolutionarily conserved functional domains. Hum. Mol. Genet. 2000, 9, 703–712, doi:10.1093/hmg/9.5.703.DeBonis, S.; Neumann, E.; Skoufias, D. Self protein-protein interactions are involved in TPPP/p25 mediated microtubule bundling. Sci. Rep. 2015, 5, 13242, doi:10.1038/srep13242.
  24. Kim, M.H.; Cierpicki, T.; Derewenda, U.; Krowarsch, D.; Feng, Y.; Devedjiev, Y.; Dauter, Z.; Walsh, C.A.; Otlewski, J.; Bushweller, J.H.; et al. The DCX-domain tandems of doublecortin and doublecortin-like kinase. Nat. Struct. Biol. 2003, 10, 324–333, doi:10.1038/nsb918.Oláh, J.; Szénási, T.; Szabó, A.; Kovács, K.; Lőw, P.; Štifanić, M.; Orosz, F. Tubulin binding and polymerization promoting properties of TPPP proteins are evolutionarily conserved. Biochemistry 2017, 56, 1017–1024, doi:10.1021/acs.biochem.6b00902.
  25. Reiner, O.; Coquelle, F.M.; Peter, B.; Levy, T.; Kaplan, A.; Sapir, T.; Orr, I.; Barkai, N.; Eichele, G.; Bergmann, S. The evolving doublecortin (DCX) superfamily. BMC Genome 2006, 7, 188, doi:10.1186/1471-2164-7-188.Sapir, T.; Horesh, D.; Caspi, M.; Atlas, R.; Burgess, H.A. Doublecortin mutations cluster in evolutionarily conserved functional domains. Hum. Mol. Genet. 2000, 9, 703–712, doi:10.1093/hmg/9.5.703.
  26. Wiser, M.F. Apicomplexa. https://www.tulane.edu/~wiser/protozoology/notes/api.html Kim, M.H.; Cierpicki, T.; Derewenda, U.; Krowarsch, D.; Feng, Y.; Devedjiev, Y.; Dauter, Z.; Walsh, C.A.; Otlewski, J.; Bushweller, J.H.; et al. The DCX-domain tandems of doublecortin and doublecortin-like kinase. Nat. Struct. Biol. 2003, 10, 324–333, doi:10.1038/nsb918.
  27. World Health Organization. Malaria. https://www.who.int/news-room/fact-sheets/detail/malaria Reiner, O.; Coquelle, F.M.; Peter, B.; Levy, T.; Kaplan, A.; Sapir, T.; Orr, I.; Barkai, N.; Eichele, G.; Bergmann, S. The evolving doublecortin (DCX) superfamily. BMC Genome 2006, 7, 188, doi:10.1186/1471-2164-7-188.
  28. Naomi S. Morrissette; L. David Sibley; Cytoskeleton of Apicomplexan Parasites. Microbiology and Molecular Biology Reviews 2002, 66, 21-38, 10.1128/mmbr.66.1.21-38.2002.Leung, J.M.; Nagayasu, E.; Hwang, Y.C.; Liu, J.; Pierce, P.G.; Phan, I.Q.; Prentice, R.A.; Murray, J.M.; Hu, K. A double-cortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin polymers. BMC Mol. Cell Biol. 2020, 21, 8, doi:10.1186/s12860-020-0249-5.
  29. Ke Hu; David Roos; John M. Murray; A novel polymer of tubulin forms the conoid of Toxoplasma gondii. Journal of Cell Biology 2002, 156, 1039-1050, 10.1083/jcb.200112086.Nagayasu, E.; Hwang, Y.C.; Liu, J.; Murray, J.M.; Hu, K. Loss of a doublecortin (DCX)-domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion. Mol. Biol. Cell 2017, 28, 411–428, doi:10.1091/mbc.E16-08-0587.
  30. Nicolas Dos Santos Pacheco; Nicolò Tosetti; Ludek Koreny; Ross F. Waller; Dominique Soldati-Favre; Evolution, Composition, Assembly, and Function of the Conoid in Apicomplexa. Trends in Parasitology 2020, 36, 688-704, 10.1016/j.pt.2020.05.001.Chakrabarti, M.; Joshi, M.; Kumari, G.; Singh, P.; Shoaib, R.; Munjal, A.; Kumar, V.; Behl, A.; Abid, M.; Garg, S.; et al. Inter-action of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival. Sci. Rep. 2021, 11, 4688, doi:10.1038/s41598-021-83513-5.
  31. Jacqueline M. Leung; Eiji Nagayasu; Yu-Chen Hwang; Jun Liu; Phillip G. Pierce; Isabelle Q. Phan; Robin A. Prentice; John M. Murray; Ke Hu; A doublecortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin polymers. BMC Molecular and Cell Biology 2020, 21, 1-25, 10.1186/s12860-020-0249-5.Chakrabarti, M.; Garg, S.; Rajagopal, A.; Pati, S.; Singh, S. Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion. Dis. Models Mech. 2020, 13, dmm042820, doi:10.1242/dmm.042820.
  32. Malabika Chakrabarti; Nishant Joshi; Geeta Kumari; Preeti Singh; Rumaisha Shoaib; Akshay Munjal; Vikash Kumar; Ankita Behl; Mohammad Abid; Swati Garg; et al.Sonal GuptaShailja Singh Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival. Scientific Reports 2021, 11, 1-16, 10.1038/s41598-021-83513-5.Swapna, L.S.; Parkinson, J. Genomics of apicomplexan parasites. Crit. Rev. Biochem. Mol. Biol. 2017, 52, 254–273, doi:10.1080/10409238.2017.1290043.
  33. Malabika Chakrabarti; Swati Garg; Ayana Rajagopal; Soumya Pati; Shailja Singh; Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion. Disease Models & Mechanisms 2020, 13, dmm042820, 10.1242/dmm.042820.
  34. Ferenc Orosz; Apicortin, a Constituent of Apicomplexan Conoid/Apical Complex and Its Tentative Role in Pathogen—Host Interaction. Tropical Medicine and Infectious Disease 2021, 6, 118, 10.3390/tropicalmed6030118.
  35. Swapna, L.S.; Parkinson, J. Genomics of apicomplexan parasites. Crit. Rev. Biochem. Mol. Biol. 2017, 52, 254–273, doi:10.1080/10409238.2017.1290043.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Feedback