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1987 Fiscal Year Final Research Report Summary

Studies on the Biosynthesis and Membrane integration of Cytochrome P-450.

Research Project

Project/Area Number 61480466
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 代謝生物化学
Research InstitutionKyushu University

Principal Investigator

OMURA Tsuneo  Kyushu University, Graduate School of Medical Science, Professor, 大学院医学系研究科, 教授 (80029933)

Project Period (FY) 1986 – 1987
KeywordsCytochrome P-450 / Membrane integration / Mitochondria / ミクロゾーム
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.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Hidefumi Yoshioka: Journal of Biological Chemistry. 262. 1706-1711 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ken-ichirou Morohashi: Journal of Biochemistry. 101. 879-887 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ken-ichirou Morohashi: Journal of Biochemistry. 102. 559-568 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shigeki Furuya: Journal of Biochemistry. 102. 821-832 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeo Kumamoto: Journal of Biochemistry. 102. 833-838 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshihide Hashimoto: Journal of Biochemistry. 103. 487-492 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Weijia Ou, et al.: "Processing-independent In Vitro Translocation of Cytochrome P-450(SCC) Precursor across Mitochondrial Membranes." Journal of Biochemistry. 100. 1287-1296 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsumi Matsumoto, et al.: "Purification and Charaterization of Three Male-specific and One Female-specific Forms of Cytochrome P-450 from rat Liver Microsomes." Journal of Biochemistry. 100. 1359-1371 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hidefumi Yoshioka, et al.: "Structural Analysis and Specific Expression of Microsomal Cytochrome P-450(M-1) mRNA in Male Rat Livers." Journal of Biological Chemistry. 262. 1706-1711 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shigeki Furuya, et al.: "Synthetic Partial Extension Peptides of P-450(SCC) and Adrneodoxin Precursors: Effects on the Import of Mitochondrial Enzyme Precursors." Journal of Biochemistry. 102. 821-832 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeo Kumamoto, et al.: "Site-directed Mutagenesis of Basic Amino Acid Residues in the Extension Peptide of P-450(SCC) Precursor: Effects on the Import of the Precursor into Mitochondria." Journal of Biochemistry. 102. 833-838 (1987)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1989-03-30  

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