In the past decade, protein fragments acting in the disruption of interfaces have been evidenced, and are named the tilted or oblique peptides. Tilted peptides are short protein fragments able to destabilize lipid membranes. Tilted peptides can be function al protein motif involved in protein/membrane fusion processes and in other biological events related to the disruption of a hydrophilic/hydrophobic interface. In this program we aspire to obtain a fundamental understanding of the tilted peptides and their involvement in membrane fusion. In order to better understand the relationships between their lipid-destabilising activity and their properties, we will study the biophysical properties of four peptides (three tilted peptides and one non tilted peptide) with different techniques. With this mission we aim to uncover general principles that govern the structure and dynamics of tilted membrane peptides and to obtain a fundamental understanding of their architecture in relation to their function.
In particular, we will analyse the role of tilted peptide/lipid interactions in determining properties of proteins in membranes via an experimental approach using model membrane systems. We expect that our studies will provide new insight into the structure, function and dynamics of membrane proteins and how this is modulated by the lipid environment. The project will build on the knowledge and expertise that has been gained over the years in the laboratory in studying different aspects of protein-lipid interactions. This expertise ranges from advanced biophysical techniques to modern molecular biological approaches and from model membrane systems to intact biological membranes. For the synthesis of the peptides we will continue the longstanding collaboration with Prof. Liskamp. Most of the approaches we intend to us, such as wide-line solid state NMR, CD, DSC are available in-house. The mass spectrometry analysis will be done in collaboration with Prof. Heck.
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