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Structural study of the interaction between the mitochondrial presequence of cytochrome c oxidase subunit IV and
A Colotto1, I Martin, J M Ruysschaert
1Department of Biochemistry, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada.
Abstract:
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 presequence causes the disordering of the liposomes containing negatively charged lipids, without destabilizing the bilayer structure or destroying the multilamellar nature of the liposomes. In the systems containing only zwitterionic lipids, a small increase in the d-spacing (lamellar stacking spacing) is observed without any disorder effect suggesting a weaker interaction of the peptide and lipid. Circular Dichroism measurements of the peptide, in the presence and absence of the different lipid systems studied, show that the secondary structure of the peptide is modulated by the lipid environment. Considerable amounts of alpha-helix in the presequence is only observed in the systems containing negatively charged lipids. These are the same systems for which the disordering effect is observed with X-ray diffraction. It is proposed 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 determining how the peptide interacts with the lipid and affects its structural organization. It is suggested that the lipid properties relevant for the disordering effect induced by the peptide are the same as those involved in the formation of contact sites between mitochondrial membranes during the import of nuclear coded proteins.
Insights
The cytochrome oxidase subunit IV presequence (p25) disorders liposomes with negative lipids by corrugating membranes, while interacting weakly with zwitterionic lipids. This peptide-lipid interaction influences mitochondrial membrane contact sites.
Area of Science:
- Biophysics
- Structural Biology
- Membrane Biology
Background:
- The presequence of cytochrome oxidase subunit IV (p25) plays a role in mitochondrial protein import.
- Understanding peptide-lipid interactions is crucial for deciphering membrane organization and function.
Purpose of the Study:
- To investigate the structural impact of the p25 presequence on multilamellar liposomes with varying lipid compositions.
- To elucidate the relationship between lipid properties and peptide-induced structural changes.
Main Methods:
- X-ray diffraction and electron microscopy were employed to analyze liposome structure.
- Circular Dichroism spectroscopy was used to study peptide secondary structure in different lipid environments.
Main Results:
- p25 induced disordering in liposomes with negatively charged lipids, without bilayer destabilization.
- A minor increase in d-spacing was observed in zwitterionic lipid systems, indicating weaker peptide-lipid interaction.
- The peptide's alpha-helical content increased significantly in negatively charged lipid systems, correlating with observed disordering.
Conclusions:
- The p25 presequence disorders liposome stacking by corrugating membranes, with effects dependent on lipid charge.
- Lipid properties, such as charge and phase behavior, dictate peptide interaction and structural effects.
- The findings suggest a link between peptide-induced membrane disordering and the formation of mitochondrial contact sites.