Development of platforms to study transmembrane proteins - towards medical, agricu...
| Grant number: | 10/01362-5 |
| Support type: | Regular Research Grants |
| Duration: | May 01, 2010 - April 30, 2012 |
| Field of knowledge: | Biological Sciences - Biophysics |
| Principal Investigator: | Claudia Elisabeth Munte |
| Grantee: | Claudia Elisabeth Munte |
| Home Institution: | Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil |
Abstract
Lipidic microdomains are specific regions in biological membranes characterized by areas rich in saturated phospholipids, sphingolipids and cholesterol. These environments play important regulatory roles in living cells, including the transport of molecules and signal transduction. While several normal proteins are found to these areas, such as Caveolins and TNFR-1, microdomains are also preferential sites for the formation of pathological forms of beta-amyloid peptides (Abeta), an important factor associated with the progression of Alzheimer disease. In the laboratory, microdomain models can be generated by combining both long and short lipid chains and, in more sophisticated models, sphingolipids and cholesterol to form bicelles. Despite bicelles tend to orient in high magnetic fields, small bicelles in certain temperatures can be observed in isotropic phase. In this project small bicelles composed by saturated phospholipids of short and long-chains will be used, either with cholesterol and sphingolipids or without. Samples will be characterized by high resolution Nuclear Magnetic (1H, 31P) and Electronic Paramagnetic Resonance spectroscopy in various concentrations and temperatures, and their integrity will be confirmed by Electronic Microscopy and/or Atomic Force Microscopy. We propose to extend this study to the interaction of such isotropic bicelles to protein and peptides, potentially the Abeta peptides related to Alzheimer disease and to the fatty-acid binding proteins FABPs. (AU)