Studies on the Biosynthesis and Membrane integration of Cytochrome P-450.
| Project/Area Number |
61480466
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
代謝生物化学
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| Research Institution | Kyushu University |
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Principal Investigator |
OMURA Tsuneo Kyushu University, Graduate School of Medical Science, Professor, 大学院医学系研究科, 教授 (80029933)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1987: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1986: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | Cytochrome P-450 / Membrane integration / Mitochondria / ミクロゾーム / チトクロームPー450 |
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| Research Abstract |
Two mitochondria-type P-450s, P-450(SCC) and P-450(11<beta>), were the main subjects of study. Their primary structures, gene structures, mechanism of import into mitochondria, and mechanism of integration into mitochondrial inner membrane were studied. Several microsomal P-450s including P-450 (M-1) and P-450(C21) were also studied.
The primary structures of the precursor peptides of P-450(SCC) and P-450)(11<beta>) were elucidated from the nucleotide sequences of the cloned cDNAs. Each of the precursor peptides has an extension peptide at the amino terminus. Various mutated precursor peptides having mutations or deletions in the extension peptide portion of in the mature peptide portion were prepared by using the cloned cDNAs. Examination of the relationship between the structures of the mutated precursors and their import into mitochondria with a cell-free system gave the conclusion that the essential part of the extension peptide is the amino terminal portion consisting of 15-20 amino acid residues. Since the precursor peptides accumulate in the matrix compartment under certain conditions, their import into mitochondria is not tightly coupled with the cleavage of the extension peptide by a processing protease. The internalized precursor peptides are loosely associated with the matrix-side surface of the inner membrane. The removal of the extension peptide by a processing protease induce the integration of the mature peptides into the inner membrane.
The essential role of the amino terminal portion of the peptide in the integration of newly synthesized peptides into the membrane is also confirmed for microsome-type P-450s. We conclude that the intracellular sorting of various forms of cytochrome P-450 is determined by relatively short amino acid sequences at the amino terminus of newly synthesized peptides.
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Report
(2 results)
Research Products
(15 results)
