Objective
A detailed understanding of the processes responsible for the failure in achieving or in maintaining the normal functional structures of proteins is of crucial importance in the development of strategies to protect or enhance human health. To gain biologic al function, polypeptide chains generally need to fold into specific three- dimensional structures - their native states. Abberrant folding of proteins can lead to a range of other scenarios, including the development of highly organised and intractable ag gregates that are deposited inside or outside cells. Such misfolding events are at the origins of a range of neurological and systemic diseases that increasingly compromise the quality and expectancy of life and the health resources of advanced societies. The focus of this application is the development of novel methods to study the structural slates of proteins that are particularly relevant to understand protein misfolding and aggregation. The species involved range from highly flexible unfolded monomers to soluble oligomers and precursors of fibrillar aggregates. In most of these states, polypeptide chains acquire structures that differ substantially from those of the native proteins that are accessible from conventional approaches of structural biology o r from structural genomics procedures. The major techniques that will be used to define at atomic level the structural characteristics of the range of species relevant to understanding misfolding and aggregation is NMR spectroscopy. In this STREP, a range of complementary NMR approaches will be developed by the various partners for this purpose. These approaches include a variety of NMR techniques and will be coupled with novel computational approaches able to define even the disorganised ensembles characte risitic of some of the most interesting and biologically relevant species. These approaches will then be applied to representative examples of the various types of proteins #
Fields of science
Not validated
Not validated
- natural sciencesbiological sciencesgenetics
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- natural sciencesphysical sciencesopticsspectroscopyabsorption spectroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein folding
- natural sciencesbiological sciencesmolecular biologystructural biology
Call for proposal
FP6-2003-LIFESCIHEALTH-I
See other projects for this call
Funding Scheme
STREP - Specific Targeted Research ProjectCoordinator
FRANKFURT/MAIN
Germany