Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor.
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Horwich AL, Kalousek F, Rosenberg LE
Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor.
Proc Natl Acad Sci U S A. 1985 Aug;82(15):4930-3.
- PubMed ID
- 3895227 [ View in PubMed]
- Abstract
Most mitochondrial proteins are encoded in the nucleus and translated in the cytoplasm as larger precursors containing NH2-terminal "leader" peptides, which are strikingly basic in overall amino acid composition. Recent experiments indicate that these leader peptides are both necessary and sufficient to direct post-translational recognition and import of precursors by mitochondria. In this report, we demonstrate a critical role for one or more of the basic arginine residues in the leader peptide of the subunit precursor for the human mitochondrial matrix enzyme, ornithine transcarbamoylase (ornithine carbamoyltransferase, carbamoylphosphate: L-ornithine carbamoyltransferase, EC 2.1.3.3). The distal three of four basic residues, all arginines, in the leader peptide of ornithine transcarbamoylase were replaced at once with charge-neutral glycine residues. The altered ornithine transcarbamoylase precursor failed to be taken up by intact mitochondria in vitro. Moreover, it also failed to be proteolytically cleaved upon incubation with a mitochondrial matrix fraction containing the Zn2+-dependent protease, which normally cleaves the leader peptide.