Mitochondrial presequences can induce aggregation of unfolded proteins.
We have studied the interactions between various synthetic peptides and two model unfolded proteins, reduced alpha-lactalbumin and reduced and carboxymethylated alpha-lactalbumin. We found that mitochondrial presequences could induce aggregation of the unfolded alpha-lactalbumins but not of the native alpha-lactalbumin. The presequence-induced aggregation of unfolded alpha-lactalbumin was dependent on electrostatic interactions and on the amphiphilicity of the presequences. Since positive charge and amphiphilicity are necessary for the targeting function of mitochondrial presequences, presequence-induced aggregation may be responsible for the instability of mitochondrial precursor proteins and may need to be inhibited by binding factors in the cytosol.
Department of Chemistry, Faculty of Science, Nagoya University, Japan.
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D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004563:Electrochemistry; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry*; D046911:Macromolecular Substances; D008745:Methylation; D008928:Mitochondria / Q000737:chemistry*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000494:pharmacology; D017510:Protein Folding; D011498:Protein Precursors / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D046911:Macromolecular Substances; D010446:Peptide Fragments; D011498:Protein Precursors; D007768:Lactalbumin; D003576:Electron Transport Complex IV