Lipidic composition effects on the mechanisms of activity and function regulation of the Na,K-ATPase.

• Grant number: 07/03435-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2009
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Biophysics - Biophysics of Processes and Systems
• Principal Investigator: Pietro Ciancaglini
• Grantee: Carolina Fortes Rigos
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The Project aims to correlate the activity control mechanisms of Na,K-ATPase with the intermolecular organization (oligomerization/aggregation) and the phase state of the membrane lipids. The enzyme activity modulation will be studied in different lipidic microenvironments (cholesterol, phospholipids and esphingolipids) as a regulation and a transduction mechanism between enzymes which do not share common metabolic intermediates (biosignalization). Also, to correlate these possible states with the solubilized and reconstituted enzymes in lipossomes and to determine bond kinetic parameters.It should be noted that in previous works it was shown that the Na,K-ATPase can be affected by ganglyosides and other glycoesphyngolipids, which, in small proportions, induce considerable changes in the mesomorphic and topological states of phospholipids in biomembranes.Due to the dependence of ATPase activity on its conformational state, its oligomerization state as well as lipids organization, it is very likely that its activity modulation may occur due to the effect that these lipids and/or enzymes cause on the structure and interface dynamic of the membrane neighbor to the Na,K-ATPase. These effects have not been studied up to the now with an integrated Biochemical-Biophysical focus.It is an original multidiscipline research Project, with scientific development potential for al researchers involved. Besides that, it can bring considerable benefits to the human resource development with more originality resulting from the combination and interchange of different concept approaches and complementary methodology ( CD, fluorescence, calorimetry, enzymatic kinetics, light scattering – all these techniques are available in our chemistry lab at FFCLRP).