Effects of model extension peptides containing glycine, proline and serine residues on the import of mitochondrial enzyme precursors into mitochondria.
We found previously that Ac-(Leu-Leu-Ala-Arg-Leu)3-NHCH3 (5(3)), a model of the extension peptide of cytochrome P-450(SCC) precursor, strongly inhibited the import of the precursor into mitochondria. Unexpectedly, however, 5(3) showed the break of respiratory control of mitochondria. In the present study, desAc- [Pro7, Ser10] 5(3) (1), [Pro7, Ser10] 5(3) (2), desAc- [Gly5, Pro7, Ser10] 5(3) (3) and [Gly5, Pro7, Ser10] 5(3) (4) were synthesized in order to investigate the influence of the Gly, Pro and Ser residues, which are present in the extension peptide, on the import and respiration. CD measurement indicated that all the peptides had an alpha-helical conformation in the presence of DPPC-DPPG (3:1) liposomes. The order of the content of alpha-helical conformation was 5(3) greater than 1, 2 greater than 3, 4, while SEP1-15 (N-terminal 1-15 fragment of the extension peptide of cytochrome P-450(SCC) precursor) showed no alpha-helical structure. The measurements of dye-leakage from liposomes, import-inhibition of P-450(SCC) and adrenodoxin precursors and respiratory inhibition of mitochondria indicated that 3 and 4, rather than 1 and 2, are similar to SEP1-15, and that the glycine residue in the extension peptide is of considerable importance for the import of the precursors.
Park
N G
NG
Kyushu University, Japan.
Aoyagi
H
H
Lee
S
S
Kato
T
T
Jinkawa
S
S
Ou
W
W
Ito
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D002942:Circular Dichroism; D005998:Glycine; D008826:Microbial Sensitivity Tests; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011392:Proline; D011487:Protein Conformation; D051381:Rats; D012694:Serine
D000900:Anti-Bacterial Agents; D010455:Peptides; D012694:Serine; D011392:Proline; D005998:Glycine