About: Role of the 14-3-3 protein in the regulation of phosducin function     Goto   Sponge   NotDistinct   Permalink

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  • Hlavním cílem je studium strukturní podstaty regulace funkce fosducinu prostřednictvím interakce s proteinem 14-3-3. Hlavními nástroji studia budou metody fluorescenční spektroskopie, analytické ultracentrifugace a proteinové krystalografie. Fosducin je protein, který se specificky a s vysokou afinitou váže na Gtβg heterodimer a inhibuje jeho interakci s Gtα podjednotkou G-proteinu či jinými efektory. Fosducin tak tlumí odpověď fotoreceptorů na světelný signál. Funkce fosducinu je inhibována fosforylací Ser54 a Ser73 a následnou vazbou regulačního proteinu 14-3-3. Detailní mechanismus tohoto procesu je neznámý. Proto navrhujeme provést detailní studium struktury komplexu 14-3-3/fosducin a zjistit, které oblasti fosducinu interagují se 14-3-3 a tím mechanisticky vysvětlit inhibiční vliv 14-3-3 na funkci fosducinu. Výsledky tohoto projektu umožní nejen lépe porozumět roli proteinu 14-3-3 v regulaci fosducinu (a v regulaci G-proteinové signalizace), ale i funkci proteinu 14-3-3 samotného.
  • The main goal is to study the structural basis for the 14-3-3 protein-dependent regulation of phosducin function. Methods of fluorescence spectroscopy, analytical ultracentrifugation and protein crystallography will be used as principal tools. Phosducin specifically binds with high affinity to Gtβg heterodimer and inhibits its interaction with Gtα or other effectors. Thus phosducin down-regulates the light response in photoreceptors. Phosducin function is regulated through the phosphorylation at Ser54 and Ser73 and the binding to the regulatory 14-3-3 protein. The detailed mechanism of the 14-3-3 protein-dependent inhibition of phosducin function is unknown. We propose to perform structural studies of the 14-3-3/phosducin complex, to identify phosducin regions involved in the interaction with 14-3-3 and thus to mechanistically explain the inhibitory role of 14-3-3 in phosducin regulation. The proposed research will increase our understanding concerning not only the role of the 14-3-3 protein in phosducin regulation (and G protein signaling) but the 14-3-3 protein function in general as well. (en)
Title
  • Role of the 14-3-3 protein in the regulation of phosducin function (en)
  • Úloha proteinu 14-3-3 na regulaci funkce fosducinu
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  • GAP305/11/0708
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  • 14-3-3 phosducin structure fluorescence crystallography phosphorylation (en)
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