Evidence of the presence of a calmodulin-sensitive plasma membrane Ca 2+ -ATPase in Trypanosoma equiperdum
| Autor: | Gustavo Benaim, María Carolina Pérez-Gordones, J. R. Ramírez-Iglesias, M. Mendoza, Vincenza Cervino, Graciela L. Uzcanga |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification 030102 biochemistry & molecular biology biology Calmodulin Peptide biology.organism_classification Transmembrane protein Amino acid 03 medical and health sciences 030104 developmental biology Biochemistry chemistry biology.protein Trypanosoma equiperdum Phosphorylation Plasma membrane Ca2+ ATPase Parasitology Molecular Biology Intracellular |
| Zdroj: | Molecular and Biochemical Parasitology. 213:1-11 |
| ISSN: | 0166-6851 |
| DOI: | 10.1016/j.molbiopara.2017.02.001 |
| Popis: | Trypanosoma equiperdum belongs to the subgenus Trypanozoon, which has a significant socio-economic impact by limiting animal protein productivity worldwide. Proteins involved in the intracellular Ca2+ regulation are prospective chemotherapeutic targets since several drugs used in experimental treatment against trypanosomatids exert their action through the disruption of the parasite intracellular Ca2+ homeostasis. Therefore, the plasma membrane Ca2+-ATPase (PMCA) is considered as a potential drug target. This is the first study revealing the presence of a PMCA in T. equiperdum (TePMCA) showing that it is calmodulin (CaM) sensitive, revealed by ATPase activity, western-blot analysis and immuno-absorption assays. The cloning sequence for TePMCA encodes a 1080 amino acid protein which contains domains conserved in all PMCAs so far studied. Molecular modeling predicted that the protein has 10 transmembrane and three cytoplasmic loops which include the ATP-binding site, the phosphorylation domain and Ca2+ translocation site. Like all PMCAs reported in other trypanosomatids, TePMCA lacks a classic CaM binding domain. Nevertheless, this enzyme presents in the C-terminal tail a region of 28 amino acids (TeC28), which most likely adopts a helical conformation within a 1-18 CaM binding motif. Molecular docking between Trypanosoma cruzi CaM (TcCaM) and TeC28 shows a significant similarity with the CaM-C28PMCA4b reference structure (2kne). TcCaM-TeC28 shows an anti-parallel interaction, the peptide wrapped by CaM and the anchor buried in the hydrophobic pocket, structural characteristic described for similar complexes. Our results allows to conclude that T. equiperdum possess a CaM-sensitive PMCA, which presents a non-canonical CaM binding domain that host a 1-18 motif. |
| Databáze: | OpenAIRE |
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