Biochemical and Biophysical Research Communications, Nov 1, 1996
The effect of calmodulin on the associative properties of D-glyceraldehyde-3-phosphate dehydrogen... more The effect of calmodulin on the associative properties of D-glyceraldehyde-3-phosphate dehydrogenase was investigated by means of a covalently attached fluorescent probe. We found that calmodulin shifts the equilibrium between the different forms of glyceraldehyde-3-phosphate dehydrogenase and binds to the subunits with an apparent dissociation constant of 1.8 mM. Within this heterologous complex calmodulin has no effect on the catalytic activity of the enzyme. The formation of the heterocomplex can be modulated by the specific anti-calmodulin drug, trifluoperazine, as well as by aldolase. The possible role of these associations is that they influence the interaction of both glyceraldehyde-3-phosphate dehydrogenase and calmodulin with other soluble proteins or structural elements. ᭧ 1996 Academic Press, Inc. Calmodulin (CaM) is a Ca 2/-dependent regulatory protein, involved in the regulation of numerous Ca 2/-mediated events [1-5]. This ubiquitous protein is present in most, if not all, cells and appears to be primarily located in the soluble fraction, however, its binding to other soluble or structural proteins is also important [6]. CaM has no inherent enzymatic activity: nevertheless, a number of enzymes (e.g. phosphodiesterase, myosin light chain kinase, calcineurin, etc.) are stimulated, while others (e.g. glycolytic enzymes phosphofructokinase and aldolase (EC. 4.1.2.13) [7-10]) are inhibited by CaM in Ca 2/ concentration dependent manner. CaM regulates up to 30 different enzymes, therefore, its role in the control of metabolic processes is evident [2-5, 10-13]. The CaM concentration varies with cell types; it is 38 mg/ kg tissue in muscle, 500 mg/kg tissue in brain [3]. Because the effect of CaM depends on the Ca 2/ concentration, which varies over a wide range, especially in muscle cells, it was suggested that CaM may act as modulator protein on dynamic enzyme associations [7, 9]. D-glyceraldehyde-3-phosphate dehydrogenase (GAPD) (EC 1.2.1.12) is a tetrameric enzyme that is present in relatively high concentration in many cell types; 14,600 mg/kg tissue in muscle, 950 mg/kg issue in brain [14]. It can reversibly dissociate into dimers and monomers on dilution [15] and in the presence of specific metabolites (e.g. ATP or D-glyceraldehyde-3phosphate) [16]. It has been demonstrated by different methods that the dimeric form of GAPD is predominantly involved in different heterologous associations [17], including its interaction with aldolase [18, 19]. In this paper we investigated the interaction between CaM and GAPD, by means of a covalently bound fluorescent probe and by using a kinetic approach and characterized the effects of aldolase and trifluoperazine (TFP) on the heterologous complex formation.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
A rapid extraction method followed by high-performance liquid chromatographic assay was developed... more A rapid extraction method followed by high-performance liquid chromatographic assay was developed for the quantitative determination of the cardioactive glycosides of Digitalis lanata. The leaf samples were extracted with water or aqueous alcohols. The simple extraction method gives a better yield than the methods described previously. Lanatoside C and its metabolites have been separated on a reversed-phase column with various mixtures of acetonitrile, methanol, and water as mobile phases for isocratic elution. Extraction and quantitative determination of lanatoside C and digoxin from a leaf sample require not more than 30 min.
The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and... more The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of the microtubule system and plays a crucial role in differentiation of oligodendrocytes. Here we first demonstrated by multinuclear NMR that the extended disordered segments are localized at the N-and C-terminals straddling a flexible region. We showed by affinity chromatography, fluorescence spectroscopy and circular dichroism that GTP binds to TPPP/p25 likely within the flexible region; neither positions nor intensities of the peaks in the assigned terminals were affected by GTP. In addition, we demonstrated that TPPP/p25 specifically hydrolyses GTP in an Mg 2+-dependent manner. The GTPase activity is comparable with the intrinsic activities of small G proteins suggesting its potential role in multiple physiological processes.
In a Hungarian family with triosephosphate isomerase (TPI; D-gll aldehyde-3-phosphate keto-isomer... more In a Hungarian family with triosephosphate isomerase (TPI; D-gll aldehyde-3-phosphate keto-isomerase, EC 5.3.1.1) deficiency, germ-line identical, but phenotypically differing compound hel zygote brothers (one of them with neurological disorder) have I identified with the same very low ( brother without neurological d der > normal control. This distinct microcompartmentation of mi proteins may be relevant in the development of the neurodeger tive process in TPI deficiency and in other, more common neurolo diseases.
Genome and transcriptome assembly data often contain DNA and RNA contaminations from external org... more Genome and transcriptome assembly data often contain DNA and RNA contaminations from external organisms, introduced during nucleotide extraction or sequencing. In this study, contamination of seed plant (Spermatophyta) transcriptomes/genomes with p25alpha domain encoding RNA/DNA was systematically investigated. This domain only occurs in organisms possessing a eukaryotic flagellum (cilium), which seed plants usually do not have. Nucleotide sequences available at the National Center for Biotechnology Information website, including transcriptome shotgun assemblies (TSAs), whole-genome shotgun contigs (WGSs), and expressed sequence tags (ESTs), were searched for sequences containing a p25alpha domain in Spermatophyta. Despite the lack of proteins containing the p25alpha domain, such fragments or complete mRNAs in some EST and TSA databases were found. A phylogenetic analysis showed that these were contaminations whose possible sources were microorganisms (flagellated fungi, protists) a...
The unicellular, parasitic fungi of the phylum Sanchytriomycota (sanchytrids) were discovered a f... more The unicellular, parasitic fungi of the phylum Sanchytriomycota (sanchytrids) were discovered a few years ago. These unusual chytrid-like fungi parasitize algae. The zoospores of the species of the phylum contain an extremely long kinetosome composed of microtubular singlets or doublets and a non-motile pseudocilium (i.e., a reduced posterior flagellum). Fungi provide an ideal opportunity to test and confirm the correlation between the occurrence of flagellar proteins (the ciliome) and that of the eukaryotic cilium/flagellum since the flagellum occurs in the early-branching phyla and not in terrestrial fungi. Tubulin polymerization promoting protein (TPPP)-like proteins, which contain a p25alpha domain, were also suggested to belong to the ciliome and are present in flagellated fungi. Although sanchytrids have lost many of the flagellar proteins, here it is shown that they possess a DNA sequence possibly encoding long (animal-type) TPPP, but not the fungal-type one characteristic of...
TPPP (tubulin polymerization promoting protein)-like proteins contain one or more p25alpha (Pfam0... more TPPP (tubulin polymerization promoting protein)-like proteins contain one or more p25alpha (Pfam05517) domains. TPPP-like proteins occur in different types as determined by their length (e.g., long-, short-, truncated-, and fungal-type TPPP) and include the protein apicortin, which possesses another domain, doublecortin (DCX, Pfam 03607). These various TPPP-like proteins are found in various phylogenomic groups. In particular, short-type TPPPs and apicortin are well-represented in the Myzozoa, which include apicomplexans and related taxa, chrompodellids, dinoflagellates, and perkinsids. The long-, truncated-, and fungal-type TPPPs are not found in the myzozoans. Apicortins are found in all apicomplexans except one piroplasmid species, present in several other myzozoans, and seem to be correlated with the conoid and apical complex. Short-type TPPPs are predominantly found in myzozoans that have flagella, suggesting a role in flagellum assembly or structure.
TPPP proteins exhibiting microtubule stabilizing function constitute a eukaryotic protein superfa... more TPPP proteins exhibiting microtubule stabilizing function constitute a eukaryotic protein superfamily, characterized by the presence of the p25alpha domain of various lengths. Vertebrate species possess three TPPP paralogs; all of them possess a full-length p25alpha domain of 160–170 amino acids and are encoded by three exons. Species of Endopterygota (Holometabola) have, besides a full-size TPPP ortholog, a protein with a truncated p25alpha domain as well, where the last coding exon, responsible for microtubule binding, is missing. It is not the result of an alternative splicing but is coded by another gene. In Drosophila melanogaster, they are named as CG45057 (long-type) and CG6709 (truncated). The truncated protein has been found in the Endopterygota orders Diptera, Coleoptera, Hymenoptera, Lepidoptera and Raphidioptera. In Lepidoptera, in several superfamilies (Gelechioidea, Bombycoidea, Noctuoidea, Pyraloidea) two paralogs of the truncated TPPP occur. Truncated orthologs (CG67...
TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfam... more TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfamily, characterized by the presence of the p25alpha domain. TPPPs in the strict sense are present in animals except Trichoplax adhaerens, which instead contains apicortin where a part of the p25alpha domain is combined with a DCX domain. Apicortin is absent in other animals and occurs mostly in the protozoan phylum, Apicomplexa. A strong correlation between the occurrence of p25alpha domain and that of the eukaryotic cilium/flagellum was suggested. Species of the deeper branching clades of Fungi possess flagellum but others lost it thus investigation of fungal genomes can help testing of this suggestion. Indeed, these proteins are present in early branching Fungi. Both TPPP and apicortin are present in Rozellomycota (Cryptomycota) and Chytridiomycota, TPPP in Blastocladiomycota, apicortin in Neocallimastigomycota, Monoblepharomycota and the non-flagellated Mucoromycota. Beside the "normal" TPPP occurring in animals, a special, fungal-type TPPP is also present in Fungi, in which a part of the p25alpha domain is duplicated. Dikarya, the most developed subkingdom of Fungi, lacks both flagellum and TPPPs. Thus it is strengthened that each ciliated/flagellated organism contains p25alpha domain-containing proteins while there are very few non-flagellated ones where p25alpha domain can be found.
The kinetics of dynamically interacting enzyme systems is examined, in the light of increasing ev... more The kinetics of dynamically interacting enzyme systems is examined, in the light of increasing evidence attesting to the widespread occurrence of this mode of organization in vivo. The transient time, a key phenomenological parameter for the coupled reaction, is expressed as a function of the lifetime of the intermediate substrate. The relationships between the transient time and the pseudo-first-order rate constants for the coupled reaction by the complexed and uncomplexed enzyme species are indicative of the mechanism of intermediate transfer (‘channelling’). In a dynamically interacting enzyme system these kinetic parameters are composite functions of those for the processes catalysed by the complex and by the separated enzymes. The mathematical paradigm can be extended to a linear sequence of N coupled reactions catalysed by dynamically (pair-wise) interacting enzymes.
Loss of the flagellum was an important step in the evolution of fungi. The flagellated fungi of t... more Loss of the flagellum was an important step in the evolution of fungi. The flagellated fungi of the phylum Olpidiomycota are the closest relative of the non-flagellated terrestrial fungi. There are genes encoding proteins, the occurrence of which shows a strong correlation with the incidence of the flagellum. One of these gene/protein families is “TPPP-like proteins” whose main feature is the presence of the p25alpha domain. The functional link between TPPP and flagellum has also been shown. Most of the phyla of flagellated fungi have been known to contain TPPP-like proteins but Olpidiomycota was an exception. This study demonstrates that Olpidium bornovanus, similarly to some fungi of Chytridiomycota and Blastocladiomycota, has a “fungal-type” TPPP characterized by the presence of two (a complete and an incomplete) p25alpha domains.
<p>The alignment was refined manually. Long type TPPPs: <i>Hs1, Homo sapiens</i>... more <p>The alignment was refined manually. Long type TPPPs: <i>Hs1, Homo sapiens</i> TPPP1/p25 (NP_008961); <i>Dm, Drosophila melanogaster</i> CG4893 (NP_648881); <i>Bd, Batrachochytrium dendrobatidis</i> (BDEG_06075); <i>Mb, Monosiga brevicollis</i> (Monbr1/23057); <i>Jl1, Jakoba libera</i> (EC692700*); <i>Mc, Malawimonas californiana</i> MCE00001955 (EC714749)*; <i>Os1, Oryza sativa</i> (CT849204*). Short type TPPPs: <i>Tt, Tetrahymena thermophila</i> (XP_001023601); <i>Pf, Plasmodium falciparum</i> (XP_001350760); <i>Chr1, Chlamydomonas reinhardtii</i> FAP265 (XP_001695016); <i>Tb, Trypanosoma brucei</i> (XP_844424); <i>Os2, Oryza sativa</i> (CT850609*). Apicortins: <i>Tg, Toxoplasma gondii</i> (EEA97769); <i>Sp, Spizellomyces punctatus</i> (SPPG_06588); <i>Ta, Trichoplax adhaerens</i> (XP_002111209). Proteins with partial p25alpha domain(s): <i>Chr2, Chlamydomonas reinhardtii</i> (XP_001690551); <i>Vc, Volvox carteri</i> (XP_002946586); <i>Tp, Trimastix pyriformis</i> TPE00006173 (EC840067*); <i>Tht, Thecamonas trahens</i> (AMSG_02233); <i>Hd, Hyperamoeba dachnaya</i> HDE00004089 (EC854006*); <i>Aa, Aureococcus anophagefferens</i> (EGB10333); <i>Phi, Phytophthora infestans</i> (XP_002907772); <i>Jl2, Jakoba libera</i> (EC691986*); <i>Se, Seculamonas ecuadoriensis</i> SEE00002453 (EC817264*); <i>Ng, Naegleria gruberi</i> D2VER9_NAEGR (EFC44650). Amino acid residues identical or similar in both short- <i>and</i> long-type TPPPs and in proteins containing partial p25alpha domain(s) are indicated by black background. Amino acid residues identical or similar in short- <i>or</i> long-type TPPPs and in proteins containing partial p25alpha domain(s) are indicated by grey background. The letter <i>x</i> labels the first 31–32 amino acids of partial p25alpha domains as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049276#pone-0049276-g002" target="_blank">Fig. 2</a>. Asterisks stands for the Rossmann-like motif (GXGXGXXGR). The letters <i>o</i> indicates an additional 14 aa sequence which is also missing in TPPP-like proteins which do not contain the Rossmann-like motif.</p
... 207 Christine Lund Kragh and Poul Henning Jensen 10 TPPP/p25: A New Unstructured Protein Hall... more ... 207 Christine Lund Kragh and Poul Henning Jensen 10 TPPP/p25: A New Unstructured Protein Hallmarking Synucleinopathies..... 225 Ferenc Orosz, Attila Lehotzky, Judit Olah and Judit Ovadi 11 Protein-Based Neuropathology and Molecular ...
The Hungarian Academy of Sciences (HAS, established in 1825), similar to the academies of the old... more The Hungarian Academy of Sciences (HAS, established in 1825), similar to the academies of the old Soviet bloc, ran a research network from 1950 until 2019 when it was detached from the Academy. The first research institute of the HAS was the Institute of Biochemistry, which started its operation in 1950. Its first director was Imre Szörényi (1905–1959) who lived in emigration in Kiev until he was called back to Hungary in 1950 by the Secretariat of the Hungarian Workers Party. Initially, for a few years research in the Institute was partly influenced by Lepeshinskaya's ‘New Cell Theory’ and Szörényi himself became the chair of the ‘Living Protein’ Committee of the HAS. He returned for more than two years to Kiev where he received a shared Stalin Prize in 1952 for the development of the antibiotic, Microcid. After his final return to Hungary in 1953, he was able to shape the characteristic image of the Institute of Biochemistry, making it one of the leading workshops of Hungarian...
Tubulin polymerization promoting proteins (TPPPs) constitute a eukaryotic protein family. There a... more Tubulin polymerization promoting proteins (TPPPs) constitute a eukaryotic protein family. There are three TPPP paralogs in the human genome, denoted as TPPP1-TPPP3. TPPP1 and TPPP3 are intrinsically unstructured proteins (IUPs) that bind and polymerize tubulin and stabilize microtubules, but TPPP2 does not. Vertebrate TPPPs originated from the ancient invertebrate TPPP by two-round whole-genome duplication; thus, whether the tubulin/microtubule binding function of TPPP1 and TPPP3 is a newly acquired property or was present in the invertebrate orthologs (generally one TPPP per species) has been an open question. To answer this question, we investigated a TPPP from a simple and early branching animal, the sponge Suberites domuncula. Bioinformatics, biochemical, immunochemical, spectroscopic, and electron microscopic data showed that the properties of the sponge protein correspond to those of TPPP1; namely, it is an IUP that strongly binds tubulin and induces its polymerization, provin...
Szörényi Imre (1905-1959) jelentős szerepet töltött be a magyar biokémia történetében. Aszszimilá... more Szörényi Imre (1905-1959) jelentős szerepet töltött be a magyar biokémia történetében. Aszszimilálódott zsidó értelmiségi családból származott. A budapesti egyetem orvosi karán Hári Pál tanítványaként kötelezte el magát a biokémiai kutatómunka mellett. Származása miatt diplomája megszerzése után előbb svájci és németországi emigrációba kényszerült-itthon nem számíthatott megfelelő állásra-, majd 1933-tól 1950-ig a Szovjetunióban, Kijevben dolgozott. Ekkor pártkezdeményezésre hazahívták, és megbízták az MTA Biokémiai Intézet megalapításával. Néhány hónap múlva visszalátogatott Kijevbe, ahonnan súlyos betegsége miatt csak 1953ban tért véglegesen haza. 1952-ben megosztott Sztálin-díjat kapott. 1953-tól tudta ténylegesen formálni a Biokémiai Intézet arculatát, amely munkássága nyomán a magyar biokémia egyik meghatározó műhelyévé vált. Korai halála ellenére, tanítványain keresztül is maradandó hatást gyakorolt a magyar biokémiára.
Biochemical and Biophysical Research Communications, Nov 1, 1996
The effect of calmodulin on the associative properties of D-glyceraldehyde-3-phosphate dehydrogen... more The effect of calmodulin on the associative properties of D-glyceraldehyde-3-phosphate dehydrogenase was investigated by means of a covalently attached fluorescent probe. We found that calmodulin shifts the equilibrium between the different forms of glyceraldehyde-3-phosphate dehydrogenase and binds to the subunits with an apparent dissociation constant of 1.8 mM. Within this heterologous complex calmodulin has no effect on the catalytic activity of the enzyme. The formation of the heterocomplex can be modulated by the specific anti-calmodulin drug, trifluoperazine, as well as by aldolase. The possible role of these associations is that they influence the interaction of both glyceraldehyde-3-phosphate dehydrogenase and calmodulin with other soluble proteins or structural elements. ᭧ 1996 Academic Press, Inc. Calmodulin (CaM) is a Ca 2/-dependent regulatory protein, involved in the regulation of numerous Ca 2/-mediated events [1-5]. This ubiquitous protein is present in most, if not all, cells and appears to be primarily located in the soluble fraction, however, its binding to other soluble or structural proteins is also important [6]. CaM has no inherent enzymatic activity: nevertheless, a number of enzymes (e.g. phosphodiesterase, myosin light chain kinase, calcineurin, etc.) are stimulated, while others (e.g. glycolytic enzymes phosphofructokinase and aldolase (EC. 4.1.2.13) [7-10]) are inhibited by CaM in Ca 2/ concentration dependent manner. CaM regulates up to 30 different enzymes, therefore, its role in the control of metabolic processes is evident [2-5, 10-13]. The CaM concentration varies with cell types; it is 38 mg/ kg tissue in muscle, 500 mg/kg tissue in brain [3]. Because the effect of CaM depends on the Ca 2/ concentration, which varies over a wide range, especially in muscle cells, it was suggested that CaM may act as modulator protein on dynamic enzyme associations [7, 9]. D-glyceraldehyde-3-phosphate dehydrogenase (GAPD) (EC 1.2.1.12) is a tetrameric enzyme that is present in relatively high concentration in many cell types; 14,600 mg/kg tissue in muscle, 950 mg/kg issue in brain [14]. It can reversibly dissociate into dimers and monomers on dilution [15] and in the presence of specific metabolites (e.g. ATP or D-glyceraldehyde-3phosphate) [16]. It has been demonstrated by different methods that the dimeric form of GAPD is predominantly involved in different heterologous associations [17], including its interaction with aldolase [18, 19]. In this paper we investigated the interaction between CaM and GAPD, by means of a covalently bound fluorescent probe and by using a kinetic approach and characterized the effects of aldolase and trifluoperazine (TFP) on the heterologous complex formation.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
A rapid extraction method followed by high-performance liquid chromatographic assay was developed... more A rapid extraction method followed by high-performance liquid chromatographic assay was developed for the quantitative determination of the cardioactive glycosides of Digitalis lanata. The leaf samples were extracted with water or aqueous alcohols. The simple extraction method gives a better yield than the methods described previously. Lanatoside C and its metabolites have been separated on a reversed-phase column with various mixtures of acetonitrile, methanol, and water as mobile phases for isocratic elution. Extraction and quantitative determination of lanatoside C and digoxin from a leaf sample require not more than 30 min.
The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and... more The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of the microtubule system and plays a crucial role in differentiation of oligodendrocytes. Here we first demonstrated by multinuclear NMR that the extended disordered segments are localized at the N-and C-terminals straddling a flexible region. We showed by affinity chromatography, fluorescence spectroscopy and circular dichroism that GTP binds to TPPP/p25 likely within the flexible region; neither positions nor intensities of the peaks in the assigned terminals were affected by GTP. In addition, we demonstrated that TPPP/p25 specifically hydrolyses GTP in an Mg 2+-dependent manner. The GTPase activity is comparable with the intrinsic activities of small G proteins suggesting its potential role in multiple physiological processes.
In a Hungarian family with triosephosphate isomerase (TPI; D-gll aldehyde-3-phosphate keto-isomer... more In a Hungarian family with triosephosphate isomerase (TPI; D-gll aldehyde-3-phosphate keto-isomerase, EC 5.3.1.1) deficiency, germ-line identical, but phenotypically differing compound hel zygote brothers (one of them with neurological disorder) have I identified with the same very low ( brother without neurological d der > normal control. This distinct microcompartmentation of mi proteins may be relevant in the development of the neurodeger tive process in TPI deficiency and in other, more common neurolo diseases.
Genome and transcriptome assembly data often contain DNA and RNA contaminations from external org... more Genome and transcriptome assembly data often contain DNA and RNA contaminations from external organisms, introduced during nucleotide extraction or sequencing. In this study, contamination of seed plant (Spermatophyta) transcriptomes/genomes with p25alpha domain encoding RNA/DNA was systematically investigated. This domain only occurs in organisms possessing a eukaryotic flagellum (cilium), which seed plants usually do not have. Nucleotide sequences available at the National Center for Biotechnology Information website, including transcriptome shotgun assemblies (TSAs), whole-genome shotgun contigs (WGSs), and expressed sequence tags (ESTs), were searched for sequences containing a p25alpha domain in Spermatophyta. Despite the lack of proteins containing the p25alpha domain, such fragments or complete mRNAs in some EST and TSA databases were found. A phylogenetic analysis showed that these were contaminations whose possible sources were microorganisms (flagellated fungi, protists) a...
The unicellular, parasitic fungi of the phylum Sanchytriomycota (sanchytrids) were discovered a f... more The unicellular, parasitic fungi of the phylum Sanchytriomycota (sanchytrids) were discovered a few years ago. These unusual chytrid-like fungi parasitize algae. The zoospores of the species of the phylum contain an extremely long kinetosome composed of microtubular singlets or doublets and a non-motile pseudocilium (i.e., a reduced posterior flagellum). Fungi provide an ideal opportunity to test and confirm the correlation between the occurrence of flagellar proteins (the ciliome) and that of the eukaryotic cilium/flagellum since the flagellum occurs in the early-branching phyla and not in terrestrial fungi. Tubulin polymerization promoting protein (TPPP)-like proteins, which contain a p25alpha domain, were also suggested to belong to the ciliome and are present in flagellated fungi. Although sanchytrids have lost many of the flagellar proteins, here it is shown that they possess a DNA sequence possibly encoding long (animal-type) TPPP, but not the fungal-type one characteristic of...
TPPP (tubulin polymerization promoting protein)-like proteins contain one or more p25alpha (Pfam0... more TPPP (tubulin polymerization promoting protein)-like proteins contain one or more p25alpha (Pfam05517) domains. TPPP-like proteins occur in different types as determined by their length (e.g., long-, short-, truncated-, and fungal-type TPPP) and include the protein apicortin, which possesses another domain, doublecortin (DCX, Pfam 03607). These various TPPP-like proteins are found in various phylogenomic groups. In particular, short-type TPPPs and apicortin are well-represented in the Myzozoa, which include apicomplexans and related taxa, chrompodellids, dinoflagellates, and perkinsids. The long-, truncated-, and fungal-type TPPPs are not found in the myzozoans. Apicortins are found in all apicomplexans except one piroplasmid species, present in several other myzozoans, and seem to be correlated with the conoid and apical complex. Short-type TPPPs are predominantly found in myzozoans that have flagella, suggesting a role in flagellum assembly or structure.
TPPP proteins exhibiting microtubule stabilizing function constitute a eukaryotic protein superfa... more TPPP proteins exhibiting microtubule stabilizing function constitute a eukaryotic protein superfamily, characterized by the presence of the p25alpha domain of various lengths. Vertebrate species possess three TPPP paralogs; all of them possess a full-length p25alpha domain of 160–170 amino acids and are encoded by three exons. Species of Endopterygota (Holometabola) have, besides a full-size TPPP ortholog, a protein with a truncated p25alpha domain as well, where the last coding exon, responsible for microtubule binding, is missing. It is not the result of an alternative splicing but is coded by another gene. In Drosophila melanogaster, they are named as CG45057 (long-type) and CG6709 (truncated). The truncated protein has been found in the Endopterygota orders Diptera, Coleoptera, Hymenoptera, Lepidoptera and Raphidioptera. In Lepidoptera, in several superfamilies (Gelechioidea, Bombycoidea, Noctuoidea, Pyraloidea) two paralogs of the truncated TPPP occur. Truncated orthologs (CG67...
TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfam... more TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfamily, characterized by the presence of the p25alpha domain. TPPPs in the strict sense are present in animals except Trichoplax adhaerens, which instead contains apicortin where a part of the p25alpha domain is combined with a DCX domain. Apicortin is absent in other animals and occurs mostly in the protozoan phylum, Apicomplexa. A strong correlation between the occurrence of p25alpha domain and that of the eukaryotic cilium/flagellum was suggested. Species of the deeper branching clades of Fungi possess flagellum but others lost it thus investigation of fungal genomes can help testing of this suggestion. Indeed, these proteins are present in early branching Fungi. Both TPPP and apicortin are present in Rozellomycota (Cryptomycota) and Chytridiomycota, TPPP in Blastocladiomycota, apicortin in Neocallimastigomycota, Monoblepharomycota and the non-flagellated Mucoromycota. Beside the "normal" TPPP occurring in animals, a special, fungal-type TPPP is also present in Fungi, in which a part of the p25alpha domain is duplicated. Dikarya, the most developed subkingdom of Fungi, lacks both flagellum and TPPPs. Thus it is strengthened that each ciliated/flagellated organism contains p25alpha domain-containing proteins while there are very few non-flagellated ones where p25alpha domain can be found.
The kinetics of dynamically interacting enzyme systems is examined, in the light of increasing ev... more The kinetics of dynamically interacting enzyme systems is examined, in the light of increasing evidence attesting to the widespread occurrence of this mode of organization in vivo. The transient time, a key phenomenological parameter for the coupled reaction, is expressed as a function of the lifetime of the intermediate substrate. The relationships between the transient time and the pseudo-first-order rate constants for the coupled reaction by the complexed and uncomplexed enzyme species are indicative of the mechanism of intermediate transfer (‘channelling’). In a dynamically interacting enzyme system these kinetic parameters are composite functions of those for the processes catalysed by the complex and by the separated enzymes. The mathematical paradigm can be extended to a linear sequence of N coupled reactions catalysed by dynamically (pair-wise) interacting enzymes.
Loss of the flagellum was an important step in the evolution of fungi. The flagellated fungi of t... more Loss of the flagellum was an important step in the evolution of fungi. The flagellated fungi of the phylum Olpidiomycota are the closest relative of the non-flagellated terrestrial fungi. There are genes encoding proteins, the occurrence of which shows a strong correlation with the incidence of the flagellum. One of these gene/protein families is “TPPP-like proteins” whose main feature is the presence of the p25alpha domain. The functional link between TPPP and flagellum has also been shown. Most of the phyla of flagellated fungi have been known to contain TPPP-like proteins but Olpidiomycota was an exception. This study demonstrates that Olpidium bornovanus, similarly to some fungi of Chytridiomycota and Blastocladiomycota, has a “fungal-type” TPPP characterized by the presence of two (a complete and an incomplete) p25alpha domains.
<p>The alignment was refined manually. Long type TPPPs: <i>Hs1, Homo sapiens</i>... more <p>The alignment was refined manually. Long type TPPPs: <i>Hs1, Homo sapiens</i> TPPP1/p25 (NP_008961); <i>Dm, Drosophila melanogaster</i> CG4893 (NP_648881); <i>Bd, Batrachochytrium dendrobatidis</i> (BDEG_06075); <i>Mb, Monosiga brevicollis</i> (Monbr1/23057); <i>Jl1, Jakoba libera</i> (EC692700*); <i>Mc, Malawimonas californiana</i> MCE00001955 (EC714749)*; <i>Os1, Oryza sativa</i> (CT849204*). Short type TPPPs: <i>Tt, Tetrahymena thermophila</i> (XP_001023601); <i>Pf, Plasmodium falciparum</i> (XP_001350760); <i>Chr1, Chlamydomonas reinhardtii</i> FAP265 (XP_001695016); <i>Tb, Trypanosoma brucei</i> (XP_844424); <i>Os2, Oryza sativa</i> (CT850609*). Apicortins: <i>Tg, Toxoplasma gondii</i> (EEA97769); <i>Sp, Spizellomyces punctatus</i> (SPPG_06588); <i>Ta, Trichoplax adhaerens</i> (XP_002111209). Proteins with partial p25alpha domain(s): <i>Chr2, Chlamydomonas reinhardtii</i> (XP_001690551); <i>Vc, Volvox carteri</i> (XP_002946586); <i>Tp, Trimastix pyriformis</i> TPE00006173 (EC840067*); <i>Tht, Thecamonas trahens</i> (AMSG_02233); <i>Hd, Hyperamoeba dachnaya</i> HDE00004089 (EC854006*); <i>Aa, Aureococcus anophagefferens</i> (EGB10333); <i>Phi, Phytophthora infestans</i> (XP_002907772); <i>Jl2, Jakoba libera</i> (EC691986*); <i>Se, Seculamonas ecuadoriensis</i> SEE00002453 (EC817264*); <i>Ng, Naegleria gruberi</i> D2VER9_NAEGR (EFC44650). Amino acid residues identical or similar in both short- <i>and</i> long-type TPPPs and in proteins containing partial p25alpha domain(s) are indicated by black background. Amino acid residues identical or similar in short- <i>or</i> long-type TPPPs and in proteins containing partial p25alpha domain(s) are indicated by grey background. The letter <i>x</i> labels the first 31–32 amino acids of partial p25alpha domains as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049276#pone-0049276-g002" target="_blank">Fig. 2</a>. Asterisks stands for the Rossmann-like motif (GXGXGXXGR). The letters <i>o</i> indicates an additional 14 aa sequence which is also missing in TPPP-like proteins which do not contain the Rossmann-like motif.</p
... 207 Christine Lund Kragh and Poul Henning Jensen 10 TPPP/p25: A New Unstructured Protein Hall... more ... 207 Christine Lund Kragh and Poul Henning Jensen 10 TPPP/p25: A New Unstructured Protein Hallmarking Synucleinopathies..... 225 Ferenc Orosz, Attila Lehotzky, Judit Olah and Judit Ovadi 11 Protein-Based Neuropathology and Molecular ...
The Hungarian Academy of Sciences (HAS, established in 1825), similar to the academies of the old... more The Hungarian Academy of Sciences (HAS, established in 1825), similar to the academies of the old Soviet bloc, ran a research network from 1950 until 2019 when it was detached from the Academy. The first research institute of the HAS was the Institute of Biochemistry, which started its operation in 1950. Its first director was Imre Szörényi (1905–1959) who lived in emigration in Kiev until he was called back to Hungary in 1950 by the Secretariat of the Hungarian Workers Party. Initially, for a few years research in the Institute was partly influenced by Lepeshinskaya's ‘New Cell Theory’ and Szörényi himself became the chair of the ‘Living Protein’ Committee of the HAS. He returned for more than two years to Kiev where he received a shared Stalin Prize in 1952 for the development of the antibiotic, Microcid. After his final return to Hungary in 1953, he was able to shape the characteristic image of the Institute of Biochemistry, making it one of the leading workshops of Hungarian...
Tubulin polymerization promoting proteins (TPPPs) constitute a eukaryotic protein family. There a... more Tubulin polymerization promoting proteins (TPPPs) constitute a eukaryotic protein family. There are three TPPP paralogs in the human genome, denoted as TPPP1-TPPP3. TPPP1 and TPPP3 are intrinsically unstructured proteins (IUPs) that bind and polymerize tubulin and stabilize microtubules, but TPPP2 does not. Vertebrate TPPPs originated from the ancient invertebrate TPPP by two-round whole-genome duplication; thus, whether the tubulin/microtubule binding function of TPPP1 and TPPP3 is a newly acquired property or was present in the invertebrate orthologs (generally one TPPP per species) has been an open question. To answer this question, we investigated a TPPP from a simple and early branching animal, the sponge Suberites domuncula. Bioinformatics, biochemical, immunochemical, spectroscopic, and electron microscopic data showed that the properties of the sponge protein correspond to those of TPPP1; namely, it is an IUP that strongly binds tubulin and induces its polymerization, provin...
Szörényi Imre (1905-1959) jelentős szerepet töltött be a magyar biokémia történetében. Aszszimilá... more Szörényi Imre (1905-1959) jelentős szerepet töltött be a magyar biokémia történetében. Aszszimilálódott zsidó értelmiségi családból származott. A budapesti egyetem orvosi karán Hári Pál tanítványaként kötelezte el magát a biokémiai kutatómunka mellett. Származása miatt diplomája megszerzése után előbb svájci és németországi emigrációba kényszerült-itthon nem számíthatott megfelelő állásra-, majd 1933-tól 1950-ig a Szovjetunióban, Kijevben dolgozott. Ekkor pártkezdeményezésre hazahívták, és megbízták az MTA Biokémiai Intézet megalapításával. Néhány hónap múlva visszalátogatott Kijevbe, ahonnan súlyos betegsége miatt csak 1953ban tért véglegesen haza. 1952-ben megosztott Sztálin-díjat kapott. 1953-tól tudta ténylegesen formálni a Biokémiai Intézet arculatát, amely munkássága nyomán a magyar biokémia egyik meghatározó műhelyévé vált. Korai halála ellenére, tanítványain keresztül is maradandó hatást gyakorolt a magyar biokémiára.
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