Phosphatidylserine asymmetry promotes the membrane insertion of a transmembrane helix (Biophysical Journal)

The plasma membrane (PM) contains an asymmetric distribution of lipids between the inner and outer bilayer leaflets. A lipid of special interest in eukaryotic membranes is the negatively charged phosphatidylserine (PS). In healthy cells, PS is actively sequestered to the inner leaflet of the PM, but PS redistributes to the outer leaflet when the cell is damaged or at the onset of apoptosis. However, the influence of PS asymmetry on membrane protein structure and folding are poorly understood. The pH-low insertion peptide (pHLIP) adsorbs to the membrane surface at neutral pH, but it inserts into the membrane at acidic pH.