Caracterización estructural de intermediarios del ciclo de reacción en la bomba de calcio de membrana plasmática
P-type ATPases are an important group of proteins whose function is the active transport of molecules and ions across biomembranes. They share the characteristic of presenting phosphorylated intermediates during their reaction cycle. PMCA is one of the main mechanisms that determine the homeostasis...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2019
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2941 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2941.dir/2941.PDF |
| Aporte de: |
| Sumario: | P-type ATPases are an important group of proteins whose function is the active transport of molecules and ions across biomembranes. They share the characteristic of presenting phosphorylated intermediates during their reaction cycle. PMCA is one of the main mechanisms that determine the homeostasis of cytosolic Ca2+ modulating signals as second messenger.\nThe fluorides of aluminum, beryllium and magnesium stabilize analogs of the phosphorylated intermediates. In this thesis we characterized their effect on PMCA, showing that: (1) Metal fluorides form stable complexes and inhibit the activities of PMCA. (2) The fluorescence of probes bound to the nucleotide binding site of PMCA decreases when the pump binds fluoride complexes. (3) The variation of fluorescence allows to follow the conformational changes and to study the binding mechanism of the fluoride complexes to PMCA as well as to detect the Ca2 +-ATPase activity in real time. (5) The binding of calmodulin to PMCA produces significant changes of the transmembrane segments, not modified by the metal fluorides binding, indicating that calmodulin can bind to the E2-P conformation.\nThese results constitute a significant contribution to elucidate the structure-function relationship of PMCA during the complex reaction cycle. |
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