Reuter group

Peripheral membrane binding

peripheral membrane protein anchors to a membrane

Peripheral membrane proteins bind temporarily to biological membranes. Unlike integral membrane proteins, the portion of the protein inserted into the lipids is restricted to the interfacial area . In common with integral membrane proteins they share the paucity of structural data. We have used Molecular Dynamics (MD) simulations with a simplified membrane representation (implicit model) to allow for a cost-effective investigation of the binding of a serine protease, called PR3, to lipid bilayers (Hajjar et al., Proteins, 2008). Calculations were performed in the presence of different types of lipid bilayers varying in their anionic character, using the IMM1(-GC) model from Themis Lazaridis (Lazaridis, Proteins, 2003 & 2005). Our results show that PR3 is able to bind both anionic and neutral membranes but with a preference for negatively charged lipids. Furthermore, the simulations of the binding mechanism reveal a unique membrane-binding site: the Interface Binding Site (IBS). It involves a few basic amino acids that ensure proper orientation of PR3 towards the membrane to allow for the insertion of a hydrophobic patch constituted of F165, F166, F224, L223, F184 and W218. These residues are carried by surface loops and in silico mutations abolish membrane association. More recently we have used explicit (all-atoms) bilayer models to get better insight into the interactions between the IBS of PR3 and the lipids (Broemstrup, PCCP, 2010). In particular the simulations reveal the importance of interactions between aromatic aminoacids and the cationic lipid headgroups (cation-pi interactions).