Structural analysis and amphiphilic properties of a chemically synthesized mitochondrial signal peptide.
Anionic phospholipids induce a marked conformational change in a synthetic peptide corresponding to residues 1-27 of pre-ornithine carbamyltransferase. The peptide designated, pO-(1-27)-peptide amide, becomes more alpha-helical in the presence of cardiolipin or dimyristoylphosphatidylglycerol but not in the presence of dimyristoylphosphatidylcholine. The greater helix-promoting action of anionic versus zwitterionic lipids is predicted by helix-coil transition theory. This statistical mechanical theory also predicts that a shorter peptide, N-acetyl-pO-(16-27)-peptide amide, has less helix-forming tendency, even in the presence of sodium dodecyl sulfate, despite the fact that it has a comparable number of positive charges. The N-acetyl-pO-(16-27)-peptide amide has no helical structure in buffer with or without dimyristoylphosphatidylglycerol but it has a small (5%) helical content in methanol. Thus, the ability of anionic lipids to promote helix formation requires more than the presence of cationic groups on the peptide. The angular dependence of the hydrophobic moment of the putative helical segment of pO-(1-27)-peptide amide demonstrates that any helical structure which is formed would have some amphiphilic character. The pO-(1-27)-peptide amide disrupts large lipid aggregates to form discoid micelles about 30 to 50 nm in diameter. The ability to lyse membranes into disc-shaped micelles is characteristic of peptides containing an amphiphathic helix. In the case of the mitochondrial signal peptide, this membrane-lytic behavior may contribute to the translocation of the protein into the organelle.
D002308:Cardiolipins / Q000494:pharmacology; D004134:Dimyristoylphosphatidylcholine / Q000494:pharmacology; D004792:Enzyme Precursors; D005614:Freeze Fracturing; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism*; D009954:Ornithine Carbamoyltransferase; D010715:Phosphatidylglycerols / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D021382:Protein Sorting Signals
D002308:Cardiolipins; D004792:Enzyme Precursors; D010715:Phosphatidylglycerols; D021382:Protein Sorting Signals; C002773:dimyristoylphosphatidylglycerol; D009954:Ornithine Carbamoyltransferase; D004134:Dimyristoylphosphatidylcholine