| Project/Area Number |
07044200
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Osaka University |
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Principal Investigator |
GOTO Yuji Osaka University, 大学院・理学研究科, 助教授 (40153770)
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| Co-Investigator(Kenkyū-buntansha) |
SEGAWA Shin-ichi Kwansei Gakuin University, 理学部, 教授 (70103132)
KUWAJIMA Kunihiro University of Tokoy, 大学院・理学系, 助教授 (70091444)
KAWATA Yasushi Tottori University, 工学部, 助教授 (40177697)
KATAOKA Mikio Osaka University, 大学院・理学研究科, 助教授 (30150254)
CHAN Hue Sun University of California, San Francisco, 薬学部, 助教授
FINK A.L. カリフォルニア大学, 化学生化学部, 教授
DOBSON C.M. オックスフォード大学, 化学部, 教授
DILL Ken A University of California, San Francisco, 薬学部, 教授
KIM P.S. マサチューセッツ工科大学, 生物部, 教授
DOBSON Chris M University of Oxford
FINK Anthony L University of California, Santa Cruz
KIM Peter S Massachusetts Institute of Technology
DILL Ken A. カリフォルニア大学, 薬学部, 教授
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1995: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Protein / Denaturation / Protein folding / X-ray solution scattering / Molecular chaperone / Molten globule / Circular dichroism / beta-Lactoglobulin |
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| Research Abstract |
Elucidation of the mechanisms of protein folding, by which the genetic information contained in the primary amino acid sequence of a protein is transmitted to its unique three-dimensional structure, is essential for understanding the structure and function of proteins. We carried out the International Scientific Research Program in order to clarify various problems of protein folding and obtained the following results.
1. We characterized the conformation and stability of the molten globule and related states of various proteins including cytochrome c, apomyoglobin, and alpha-lactalbumin. In particular, we used solution X-ray scattering to characterize their compactness and shape. Based on the structural properties obtained by solution X-ray scattering, general and conceptual structural images for the molten globule states are described and compared with the model obtained by nuclear magnetic resonance. The results indicate that the term "molten globule" is used to describe a wide range
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of non-native conformations, none of them completely consistent with the original definition.
2. beta-Lactoglobulin, a predominantly beta-sheet protein, is an interesting example representing inconsistency of the local and non-local secondary structure preference. We have studied the folding kinetics of beta-lactoglobulin and showed that a partly alpha-helical intermediate accumulates transiently before formation of the native beta-sheet. The results suggest that the folding of beta-lactoglobulin follows a non-hierarchical mechanism, in which non-native alpha-helical structures play important roles. The similar alpha-helical intermediate was also detected during the equilibrium unfolding transition induced by Gdn-HCl.
3. To understand the conformational features required for the substrate of GroEL,a molecular chaperone, we studied the interactions of GroEL with various conformational states of horse cytochrome c. The results indicate that the fluctuating and exposed hydrophobic clusters of the substrates are responsible for the interaction, and that the interaction is modulated by electrostatic interaction. These characteristics are similar to those of the interaction of cychrome c derivatives with negatively charged phospholipid membranes, suggesting a common mechanism. Less
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