Relationships between the orientation and the structural properties of peptides and their membrane interactions.

Physical properties of membranes, such as fluidity, charge or curvature influence
their function. Proteins and peptides can modulate those properties and
conversely, the lipids can affect the activity and/or the structure of the
former. Tilted peptides are short hydrophobic protein fragments characterized by
an asymmetric distribution of their hydrophobic residues when helical. They were
detected in viral fusion proteins and in proteins involved in different
biological processes that need membrane destabilization. Those peptides and non
lamellar lipids such as PE or PA appear to cooperate in the lipid destabilization
process by enhancing the formation of negatively-curved domains. Such highly bent
lipidic structures could favour the formation of the viral fusion pore
intermediates or that of toroidal pores. Structural flexibility appears as
another crucial property for the interaction of peptides with membranes.
Computational analysis on another kind of lipid-interacting peptides, i.e. cell
penetrating peptides (CPP) suggests that peptides being conformationally
polymorphic should be more prone to traverse the bilayer. Future investigations
on the structural intrinsic properties of tilted peptides and the influence of
CPP on the bilayer organization using the techniques described in this chapter
should help to further understand the molecular determinants of the peptide/lipid
inter-relationships.