1988 Fiscal Year Final Research Report Summary
Structure-function relationship of fibrinogen gamma chains in the polymerization of fibrin.
| Project/Area Number |
62570549
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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 |
Hematology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
YOSHIDA Nobuhiko Jichi Medical School, 医学部, 講師 (10049083)
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| Co-Investigator(Kenkyū-buntansha) |
TERUKINA Shigeharu Jichi Medical School, 医学部, 講師 (80146159)
MATSUDA Michio Jichi Medical School, 医学部, 教授 (50048980)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Abnormal fibrnogen / Polymerization site in gamma chain of fibrinogen / Calcium binding to gamma chain / Lysylendopeptidase / リシルエンドペプチダーゼ / アミノ酸置換 / フィブリノゲンのプラスミン分解とカルシウム |
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| Research Abstract |
Recently it has been shown that a fibrin gamma-chain polymerization site resides in the COOH-terminal portion and that the native tertiary gamma-chain structure in fragment D_1 is necessary for the expression of the polymerization site, but the presise regions or conformations responsible for the polymerization are not yey clarified. Abnormal fibrinogens with impaired fibrin monomer polymerization, whith is caused by abnormal gamma-chains, will provide information fore these questions, and four unrelated abnormal fibrinogens were analyzed in this study.
Fibrinogen Tochigi had an apparently higher molecular weight gamma-chain variant characterized by the replacement of gamma arginine-275 by cysteine. Fibrinogen Kyoto I had an apparently lower molecular weight gamma-chain variant characterized by the replacement of gamma asparagine-308 by lysisne. This amino acid substitution caused accelerated cleavage of fragment D_1 by plasmin in the presence of EGTA and the generation of a new plasmin cleavage site, gamma Lys 308-Gly 309 bond. Fibrinogen Osaka III had the normal calcium binding properties and showed the replacement of gamma arginine-275 by histidine.
Fibrinogen Osaka V had a gamma-chain variant characterized by the replacement of gamma arginine-375 by glycine and the defective calcium binding. This fibrinogen showed the normal thrombin time in the presence of calcium, and calcium ions can not protect fibrinogen fragment D_1 against further attack by plasmin.
These data suggest that the tertiary structure of gamma-chains in the broad range sequence spanning gamma Arg 275 to Arg 375 will be necessary for the expression of the polymerization site, although the direct binding site of amino ternimal portion of -chain remained unknown. In addition, calcium ions bound to gamma-chains does not seem to affect the ecceleration of fibrin polymerization, as is known from the normal thrombin tine of fibrinogen Osaka V in the presence of calcium.
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Research Products
(6 results)
