Structural study of the interaction between the mitochondrial presequence of cytochrome c oxidase subunit IV and model membranes

The structural effect of the presequence of cytochrome oxidase subunit IV ( p25) on multilamellar liposomes with different lipid compositions has been investigated using X-ray diffraction and electron microscopy. The presequen ce causes the disordering of the liposomes containing negatively charged li pids, without destabilizing the bilayer structure or destroying the multila mellar nature of the liposomes. In the systems containing only zwitterionic lipids, a small increase in the d-spacing (lamellar stacking spacing) is o bserved without any disorder effect suggesting a weaker interaction of the peptide and lipid. Circular Dichroism measurements of the peptide, in the p resence and absence of the different lipid systems studied, show that the s econdary structure of the peptide is modulated by the lipid environment. Co nsiderable amounts of ct-helix in the presequence is only observed in the s ystems containing negatively charged lipids. These are the same systems for which the disordering effect is observed with X-ray diffraction. It is pro posed that p25 disorders the bilayer stacking by corrugating the membranes. The results are discussed in terms of the relevance of the specific lipid properties (e.g., electric charge and ability to form inverted phases) in d etermining how the peptide interacts with the lipid and affects its structu ral organization. It is suggested that the lipid properties relevant for th e disordering effect induced by the peptide are the same as those involved in the formation of contact sites between mitochondrial membranes during th e import of nuclear coded proteins.