Peripheral membrane proteins bind temporarily to biological membranes. Unlike integral membrane proteins, the portion of the protein inserted into the lipid-bilayer is restricted to the interfacial area. In common with integral membrane proteins they share a paucity of structural data.
We are interested in understanding the detailed membrane binding mechanisms and role of different amino acids in peripheral binding.
Our investigation on serine protease (PR3) with implicit membrane model reveals that PR3 is able to bind both anionic and neutral membranes but with a preference for negatively charged lipids (Hajjar et al., Proteins, 2008). We identified a unique membrane-binding site, which contains hydrophobic patch, carried by surface loops that insert into membrane. Simulations with explicit (all-atoms) bilayer models reveal the importance of interactions between aromatic amino acids and the cationic lipid headgroups (cation-pi interactions) (Broemstrup, PCCP, 2010). Our work (experiments and simulations) reveals PR3 has higher affinity towards zwitterionic membranes compared to its homologue HNE due to partitioning of aromatic amino acids in the membrane (Schillinger et al., BBA-Biomembranes, 2014).
Using a combination of in vitro and in silico mutagenesis, we demonstrated how correlated motion in a bacterial phospholipases is important for enzymatic activity (Cheng et al., Biophys. J., 2013). Based on our investigation on a bacterial phospholipase from Bacillus thuringiensis (BtPI-PLC), we suggested that cation-pi interaction at the membrane interface might be a novel anchoring mechanism for peripheral proteins (Grauffel et al., JACS, 2013). A quantitative model for BtPI-PLC cell membrane interactions is also proposed based on the transient interaction of the protein with the membrane (Yang et al., JACS, 2015).
We are also looking at N-alpha acetyltransferse (Naa60), a subunit of one of N-terminal acetyltransferase (NAT) as a potential candidate for membrane association. Our collaborators (Thomas Arnesens group) have revealed that Naa60 show a distinctive localization to the secretory pathways and preferentially acetylates transmembrane proteins with an N-terminus facing the cytosol.