The characterization and evolutionary relationships of a trypanosomal thiolase

[Display omitted] ► Genome database screening revealed three thiolase isoforms in trypanosomatids. ► African trypanosomes contain only the SCP2-thiolase isoform. ► The expression of Trypanosoma brucei SCP2 ( TbSCP2)-thiolase is developmentally regulated. ► TbSCP2-thiolase displays activity in both t...

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Published in:International journal for parasitology 2011-10, Vol.41 (12), p.1273-1283
Main Authors: Mazet, Muriel, Harijan, Rajesh K., Kiema, Tiila-Riika, Haapalainen, Antti M., Morand, Pauline, Morales, Jorge, Bringaud, Frédéric, Wierenga, Rik K., Michels, Paul A.M.
Format: Article
Language:English
Subjects:
Acetyl-CoA C-Acyltransferase - genetics
Acetyl-CoA C-Acyltransferase - metabolism
Biological and medical sciences
Cloning, Molecular
Cluster Analysis
Computational Biology - methods
Escherichia coli
Escherichia coli - genetics
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene Expression Profiling
Humans
Isoenzymes - genetics
Isoforms
Leishmania
Leishmania - enzymology
Life cycle. Host-agent relationship. Pathogenesis
Metabolism
Mitochondria - enzymology
Mitochondrion
Phylogenetic analysis
Phylogeny
Protein Sorting Signals
Protozoa
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
SCP2
Sequence Homology, Amino Acid
Thiolase
Trypanosoma
Trypanosoma - enzymology
Trypanosoma cruzi
Trypanosomatidae
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Summary:[Display omitted] ► Genome database screening revealed three thiolase isoforms in trypanosomatids. ► African trypanosomes contain only the SCP2-thiolase isoform. ► The expression of Trypanosoma brucei SCP2 ( TbSCP2)-thiolase is developmentally regulated. ► TbSCP2-thiolase displays activity in both the degradative and synthetic directions. ► SCP2-thiolase knockdown in procyclic T. brucei does not lead to a growth phenotype. Thiolases are enzymes that remove an acetyl-coenzyme A group from acyl-CoA in the catabolic β-oxidation of fatty acids, or catalyse the reverse condensation reaction for anabolic processes such as the biosynthesis of sterols and ketone bodies. In humans, six homologous isoforms of thiolase have been described, differing from each other in sequence, oligomeric state, substrate specificity and subcellular localization. A bioinformatics analysis of parasite genomes, being (i) different species of African trypanosomes, (ii) Trypanosoma cruzi and (iii) Leishmania spp., using the six human sequences as queries, showed that the distribution of thiolases in human and each of the studied Trypanosomatidae is completely different. Only one of these isoforms, called SCP2-thiolase, was found in each of the Trypanosomatidae, whereas the TFE-thiolase was also found in T. cruzi and Leishmania spp., and the AB-thiolase only in T. cruzi. Each of the trypanosomatid thiolases clusters with its orthologues from other organisms in a phylogenetic analysis and shares with them the isoform-specific sequence fingerprints. The single T. brucei SCP2-thiolase has been expressed in Escherichia coli and characterized. It shows activity in both the degradative and synthetic directions. Transcripts of this thiolase were detected in both bloodstream- and procyclic-form trypanosomes, but the protein was found only in the procyclic form. The encoded protein has both a predicted N-terminal mitochondrial signal peptide and a C-terminal candidate type 1 peroxisomal-targeting signal for sorting it into glycosomes. However experimentally, only a mitochondrial localization was found for both procyclic trypanosomes grown with glucose and cells cultured with amino acids as an energy source. When the thiolase expression in procyclic cells was knocked down by RNA interference, no important change in growth rate occurred, irrespective of whether the cells were grown with or without glucose, indicating that the metabolic pathway(s) involving this enzyme is/are not essential for the pa
ISSN:0020-7519
1879-0135
DOI:10.1016/j.ijpara.2011.07.009