| Project/Area Number |
17360395
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biofunction/Bioprocess
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| Research Institution | Japan Advanced Institute of Science and Technology |
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Principal Investigator |
TAKAGI Masahiro Japan Advanced Institute of Science and Technology, School of Materials Science, Professor (00183434)
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| Co-Investigator(Kenkyū-buntansha) |
HOSAKA Takahiro Japan Advanced Institute of Science and Technology, School of Materials Sciences, Associate Professor (30263619)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,190,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥990,000)
Fiscal Year 2007: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | Protein / Structure / Amyloid / Membrane / Interaction / タンパク質 / フォールディング / 構造変化 / 拡張遺伝子工学 / ウシトリプシンインヒビター / ミクログロブリン |
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| Research Abstract |
(1) In order to perform analysis of protein structural alteration at single molecular level using FRET method We attempted fluorescence labeling of bavine pancreatic tripsin inhibitor (BFTI) using a new technique of four base codon method. Fluorescent proteins were obtained but not enough yield for studies at molecular level
(2) The effects of negatively charged phosphatidylserine (PS) and neutral phosphatidylcholine (PC) on the structure of wild-type and mutant bovine pancreatic trypsin inhibitor (BPTI) at neutral pH were investigated. The presence of PC did not have any effect on the protein structure whilst PS induced a non-native structure in three mutant BPTI proteins. However, the negatively charged phospholipid did not have any effect on wild-type BPTI. The findings revealed that (i) elimination of some disulphide bonds, results in dramatic change in protein structure, and, (ii) that this biochemical interaction is surface-driven and that electrostatic interactions may play a ver
… More
y strong role in influencing the fore-stated changes in protein structure.
(3) Patients on long term hemodyalysis frequently suffer from dialysis-related amyloidosis (DRA). DRA is a pathology associated with a persistent increase of monomeric β2- microglobulin (β2-m) caused by dialysis treatment of renal failure. The mechanism of formation of amyloid fibrils for this protein, as for all the other amyloidogenic proteins, is not clear, and there was great uncertainty about the molecular bases of amyloid deposition when the amyloidogenicity of β2-m was discovered. In this study, we investigated formation of variant β2-m in serum of a patient who receives treatment of hemodialysis. Variant β2-m is derived from restricted cleavage of β2-M. The possible factor involved in formation of variant β2-m was also estimated. The following conclusions are proposed. Formation of variant β2-m, namely restricted cleavage of β2-m, might be caused by proteolytic cleavage by a serum protease(s). However, it is not clear whether the variant β2-m can trigger formation of amyloid. Protein aggregation formation is enhanced in serum from a patient. Less
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