2005 Fiscal Year Final Research Report Summary
Development of Sensor System to Analyse and Diagnose the abnormality of Protein Conformation
| Project/Area Number |
15206089
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Osaka University |
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Principal Investigator |
KUBOI Ryoichi Osaka University, Dept.Eng.Sci., Professor, 大学院・基礎工学研究科, 教授 (40029567)
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| Co-Investigator(Kenkyū-buntansha) |
TSUCHIDO Tetsuaki Kansai University, Dept.Eng., Professor, 工学部, 教授 (50029295)
GOTO Yuji Osaka University, Protein Institution, Professor, 蛋白質研究所, 教授 (40153770)
UMAKOSHI Hiroshi Osaka University, Dept.Eng.Sci., Associate Professor, 大学院・基礎工学研究科, 助教授 (20311772)
YOSHIMOTO Makoto Yamaguchi University, Dept.Eng., Eng., Associate Professor, 工学部, 助教授 (80322246)
SHIMANOUCHI Toshinori Osaka University, Dept.Eng.Sci., Assistant Professor, 大学院・基礎工学研究科, 助手 (10335383)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Membrane Stress Biotechnology / Oxidative Stress / Amyloidogenic Protein / Stress Sensor / Conformational Disease / Hydrogen Bonding / Liposome / Fluctuation |
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| Research Abstract |
The goal of this research project is to establish the analytical method of dynamic interaction between the structurally abnormal protein and biomembrane under the stress condition, especially focusing on the local hydrophobicity (LH) or structural fluctuation. Amyloid beta peptide (Aβ) has been employed as a case study of the system to analyze and characterize the structural abnormality of various proteins. During past two years, we have developed the sensor system of the structural abnormality of protein and have established the database on the protein abnormality under the stress condition. In 2005, the method to judge the structural abnormality of proteins has been investigated based on the previous findings. Based on the database, the suitable conditions (stress condition and lipid compositions) to regenerate the conformational abnormality of protein under the stress condition on the liposome surface have been clarified, resulting that the microdomain-like structure of the membrane
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surface was found to play an important role on the conformational abnormality of proteins/peptides. It was furthermore found that the microdomain-like structure could suitably be controlled by the control of the stress conditions (heating, pH and ionic strength) and the modification of membrane components (alcohols, fatty acids, cholesterol). Especially in the case of the cholesterol-modified liposome, the Aβ-membrane interaction was found to be controlled on the membrane in the presence of metal ion, Cu. The Aβ-Cu complex furthermore induced the metalloenzyme-like function(oxidation of cholesterol and dopamine). The above potential functions of Aβ on the membrane was found to be closely related to the stability of hydrogen-bond of the main chain of the Aβ in the hydrophobic nano environment inside the liposome membrane. By using the membrane chip arraying various stressed-liposomes on the chip, it was found that we could assess the structural abnormality of the protein. The above findings on the structural abnormality of protein were summarized together with the physiological role of amyloid fibril formation of Aβ on the biomembrane. Less
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