Conversion of a nonprocessed mitochondrial precursor protein into one that is processed by the mitochondrial processing peptidase.
Mitochondrial processing peptidase (MPP) cleaves the signal sequence from a variety of mitochondrial precursor proteins. A subset of mitochondrial proteins, including rhodanese and 3-oxoacyl-CoA thiolase, are imported into the matrix space, yet are not processed. Rhodanese signal peptide and translated protein were recognized by MPP, as both were inhibitors of processing. The signal peptide of precursor aldehyde dehydrogenase consists of a helix-linker-helix motif but when the RGP linker is removed, processing no longer occurs (Thornton, K., Wang, Y., Weiner, H., and Gorenstein, D. G. (1993) J. Biol. Chem. 268, 19906-19914). Disruption of the helical signal sequence of rhodanese by the addition of the RGP linker did not allow cleavage to occur. However, addition of a putative cleavage site allowed the protein to be processed. The same cleavage site was added to 3-oxoacyl-CoA thiolase, but this protein was still not processed. Thiolase and linker-deleted aldehyde dehydrogenase signal peptides were poor inhibitors of MPP. It can be concluded that both a processing site and the structure surrounding this site are important for MPP recognition.
Waltner
M
M
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-1153, USA.
Weiner
H
H
D000102:Acetyl-CoA C-Acyltransferase / Q000096:biosynthesis / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D008666:Metalloendopeptidases / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D051381:Rats; D015183:Restriction Mapping; D017384:Sequence Deletion; D013884:Thiosulfate Sulfurtransferase / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic; D000096122:Mitochondrial Processing Peptidase
D000102:Acetyl-CoA C-Acyltransferase; D000444:Aldehyde Dehydrogenase; D017931:DNA Primers; D004792:Enzyme Precursors; D008666:Metalloendopeptidases; D021382:Protein Sorting Signals; D013884:Thiosulfate Sulfurtransferase; D000096122:Mitochondrial Processing Peptidase