Structural and Functional Analysis of Complement C3/C5 Convertases.
| Project/Area Number |
01570233
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
細菌学
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| Research Institution | Osaka University |
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Principal Investigator |
KINOSHITA Taroh Osaka University Medical School, Assistant Professor, 医学部, 講師 (10153165)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Kozo Osaka University Medical School, Professor, 医学部, 教授 (10028300)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Complement / Self defense / Immunity |
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| Research Abstract |
We have analyzed C5 convertase of the classical pathway and the alternative pathway of complement, and obtained following results.
(1) Within the classical pathway C5 convertase, C4b2a3b complex, C3b binds to C4b through an ester-linkage. Protein chemical analysis of C4b-C3b complex demonstrated that the C3b-binding site is within a region that spans from Ala 1186 to Lys 1259. Further localization of the binding site was achieved by using mutant C4 proteins prepared by recombinant DNA technology : Ser 1217 was found to be a primary binding site and Ser 1219 to be an alternative site. These results suggest that binding of C3b to C4b is a specific reaction to form a trimolecular complex with defined quaternary structure.
(2) C4A6 protein, A mutant C4 that does not form C5 convertase, was analyzed. It was found that C4A6 when activated makes C4b2a3b complex but this complex does not bind C5, indicating C4b also contributes in C5-binding.
(3) The alternative pathway C5 convertase was reconstituted from purified C3b dimer and factors B and D. This supports our model of the C5 convertase that holds that the alternative pathway C5 convertase is a trimolecular complex in which Bb binds noncovalently to a covalently linked C3b dimer.
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Report
(3 results)
Research Products
(10 results)
