1995 Fiscal Year Final Research Report Summary
Determination of the active site of the complement regulatory protein CD59
| Project/Area Number |
06672199
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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 |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
NAKANO Yasuko Showa University, Phrmaceutical Science, Assistant Professor, 薬学部, 助手 (20155790)
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| Project Period (FY) |
1994 – 1995
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| Keywords | CD59 / Complement / Membrane Attack Complex (MAC) / Active site / Synthetic Peptide / Complement Regulatory Protein |
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| Research Abstract |
CD59 inhibits the formation of membrane attack complex (MAC) of human complement by binding to C8 and C9 in the nascent membrane attack complex and inhibiting C9 binding to C8 in C5b-8 and C9 polymerization. Considering 5 disulfide bridges of CD59, we divided the molecule into two portions and synthesized the two peptides. One represented an amino-terminal half, P1-41, consisting of residues 1 to 41 while another represented a carboxyl-terminal half, P42-77, consisting of residues 42 to 77. P1-41 inhibited the MAC formation much more strongly than P42-77, indicating that the amino-terminal half contained the active site. We further synthesized P4-18 that consisted of residues 4 to 18 and P19-41 that consisted of residues 19 to 41. The activity of P4-18 was less than that of P19-41. Surprisingly P19-41 showed higher activity than P1-41 and was comparable to urine CD59. The residues 19 to 41 were further divided into two portions : P20-25 which consisted of residues 20 to 25 and P27-38 which consisted of residues 27 to 38. Although their activities were significantly less than the activity of P19-41, P27-38 showed higher activity than P20-25. The residues 27 to 38 were further divided into three portions ; P27-32 which consisted of residues 27 to 32, P30-34 which consisted of residues 30 to 34 and P33-38 which consisted of residues 33 to 38. When these peptides were assayd for the activities, all of them showed significant activities, even though they needed 10-fold more concentrations than P19-41. These data suggest that the residues 27 to 38 is the active site constituting the binding site to C8 and C9.
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Research Products
(2 results)
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[Publications] Nakano, Y., Tozaki, T., Kikuta, N., Tobe, T., Oda, E., Miura, N-H., Sakamoto, T.and Tomita, M.: "Determination of the active site of CD59 with synthetic peptides." Molecular Immunology. 32 (4). 241-247 (1995)
Description
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