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Molten Globule State of Proteins-Conformation, Stability, and Its Physiological Role

Research Project

Project/Area Number 05044131
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionOsaka University

Principal Investigator

GOTO Yuji  Osaka University, 理学部, 助教授 (40153770)

Co-Investigator(Kenkyū-buntansha) KAWATA Yasushi  Tottori University, 工学部, 助教授 (40177697)
KATAOKA Mikio  Osaka University, 理学部, 助教授 (30150254)
KONISHI Yasuo  National Research Council, Canada, 部門長
FINK A.l.  University of California, Santa Cruz, 化学生化学部, 教授
DILL Ken.a.  University of California, San Francisco, 薬学部, 教授
倉光 成紀  大阪大学, 理学部, 教授 (60153368)
DILL Ken A  カリフォルニア大学, 薬学部, 教授
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsProtein / Electrostatic interaction / Hydrophobic interaction / Solution X-ray scattering / Mass spectrometry / Molten globule state / Molecular chaperon / Protein folding / タンパク質 / マススペクトル / 熱ショック蛋白質 / タンパク質の構造形成
Research Abstract

The molten globule, state, a compact denatured state with significant secondary structure but a largely disordered tertiary structure, has been proposed to be a major intermediate state in protein folding and its participation in various in vivo processes has been suggested. However, much remains unknown-particularly the mechanism of conformational stability and its physiological role. We carried out the International Scientific Research Program in order to clarify these problems and obtained the following results.
1)Conformation and stability of the molten globule state Structural characteristics of various conformational state of apomyoglobin were studied by solution X-ray scattering. The results show that the molten globule state is expanded from the native state and that it contains a core comprising a cluster of helices and flaring tails. Role of hydrophobic and electrostatic interactions in stabilizing the molten globule state of apomyogobin and cytochrome c was studied by calorim … More etry and circular dichroism. It was shown that the stability of the molten globule state is critically determined by a balance of charge repulsive forces and hydrophobic forces. By comparing the various conformational states, we constructed a folding profile, which shows that the protein becomes more compact with formation of the secondary structure. The profiles are consistent with the prediction on the basis of the statistical mechanical theory.
2.Nature of substrate proteins recognized by molecular chaperons Mechanism of interaction of GroEL and substrate proteins was studied. We found that GroEL recognizes the flexible and exposed hydrophobic clusters of the substrate proteins. On the other hand, DanK was found to recognize more disordered conformational states.
3.Analysis of the molten globule state by mass spectrometry
H/D exchange reaction of the molten globule state was analyzed by electrospray mass spectrometry. It was indicated that mass spectrometry is useful to characterize the structural flexibility of the molten globule state. Less

Report

(2 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Hagihara,Y.: "Cmparison of the Conformational Stability of the Molten Globule and Natie States of Horse Cytochrome c" J.Mol.Biol.237. 336-348 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] NIshii,I.: "Cold-Denaturation of the Molten Globule States of Apomyoglobin and a Profile for Protein Folding." Biochemistry. 33. 4903-4909 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hamada,D.: "Salt-Induced Formation of the Molten Globule State of Cytochrome c Studied by Isothermal Calorimetry" Proc.Natl.Acad.Sci.U.S.A.91. 10325-10329 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hagihara,Y.: "Thermal Unfolding of Tetrameric Melittin:Comparison with the Molten Globule of Cytochrome c." Protein Sci.3. 1418-1429 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hoshino,M.: "Perchlorate-Induced Formation of the a-Helical Structure of Mastoparan." J.Biochem.116. 910-915 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shiraki,K.: "Trifluoroethanol-Induced Stabilization of the a-Helical Structure of B-Lactoglobulin." J.Mol.Biol.237. 336-348 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Dill,K.A.: "Modeling Protein Stability as Heteropolymer Collapse." Adv.Protein Chem.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fink,A.L.: "Classification of Acid Denaturation of Proteins:Intermediate and Unfolded States." Biochemistry. 33. 12504-12511 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 小西康夫: "誌上対談・質量分析法を用いた蛋白質の高次構造の研究" 蛋白質核酸酵素. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kataoka,M.: "Structural Characterization of the Molten Globule and Native States of Apomyoglobin by X-Ray Scattering." J.Mol.Biol.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kawata,Y.: "Chaperonin GroE and ADP Facilitate the Folding of Various Proteins and Protect Against Heat Inactivation." FEBS Letters. 345. 229-232 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Konishi,Y.: "Conformational Stability of Heme Proteins in Vacuo." Biochemistry. 33. 9706-9711 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Goto, Y.: "Acid-Induced Folding of Heme Proteins." Methods in Enzymology. 232. 3-15 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hagihara, Y.: "Comparison of the Conformational Stability of the Molten Globule and Native States of Horse Cytochrome c." J.Mol.Biol. 237. 336-348 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishii, I.: "Cold-Denaturation of the Molten Globule States of Apomyoglobin and a Profile of Protein Folding." Biochemistry. 33. 4903-4909 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hamada, D.: "Salt-Induced Formation of the Molten Globule State of Cytochrome c Studied by Isothermal Titration Calormetry." Proc.Natl.Acad.Sci.U.S.A.91. 10325-10329 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hagihara, Y.: "Thermal Unfolding of Tetrameric Melittin : Comparison with the Molten Globule of Cytochrome c." Protein Sci.3. 1418-1429 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shiraki, K.: "Trifluoroethanol-Induced Stabilization of the a-Helical Structure of b-Lactoglobulin." J.Mol.Biol.237. 336-348 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] De Young, L.R.: "Aggregation and Denaturation of Apomyoglobin in Aqueous Urea Solutions." Biochemistry. 32. 3877-3886 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fink, A.L.: "Classification of Acid Denaturation of Proteins : Intermediate and Unfolded States." Biochemistry. 33. 12504-12511 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Konishi, Y.: "Conformational Stability of Heme Proteins in Vacuo." Biochemistry. 33. 9706-9711 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kataoka, M.: "Structural Characterization of the Molten Globule and Native States of Apomyoglobin by Solution X-Ray Scattering." J.Mol.Biol.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kawata, Y.: "Chaperonin GroE and ADP Facilitate the Folding of Various Proteins and Protect Against Heat Inactivation." FEBS Letters. 345. 229-232 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Dill, K.A.: "Modeling Protein Stability as Heteropolymer Collapse." Adv.Protein Chem.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Seshadri,S.,Oberg,K.A. & Fink,A.L.: "Thermally Denatured Ribonuclease A Retains Secondary Structure As Shown by FTIR" Biochemistry. 33. 1351-1355 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] De Young,L.R.,Dill,K.A. & Fink,A.L.: "Aggregation and Denaturation of Apomyoglobin in Aqueous Urea Solutions." Biochemistry. 32. 3877-3886 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kubo,T.,Mizobata,T. & Kawata,Y.: "Refolding of Yeast Enolase in the Presence of the Chaperonin GroE." J.Biol.Chem.268. 19346-19351 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Flanagan,J.M.,Kataoka,M.Fujisawa,T. & Engleman,D.M.: "Mutation Can Cause Large Changes in the Conformation of A Denatured Protein." Biochemistry. 229. 10359-10370 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 片岡 幹雄: "X線溶液散乱でみたunfold状態の構造" 生物物理. 33. 31-35 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 河田 康志: "蛋白質分子の構造形成とその安定性-ペプチドからオリゴマー酵素までを例にして" 蛋白質核酸酵素. 38. 11-25 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hamada,D.,Hoshino,M.,Kataoka,M.,Fink,A.L., & Goto,Y.: "Intermediate Conformational States of Apocytochrome c." Biochemistry. 32. 10351-10358 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Goto,Y.,Hagihara,Y.,Hamada,D.,Hoshino,M. & Nishii,I.: "Acid-induced Unfolding and Refolding Transitions of Cytochrome c." Biochemistry. 32. 11878-11885 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hagihara,Y.,Tan,Y. & Goto,Y.: "Comparison of the Conformational Stability of the Molten Globule and Native States of Horse Cytochrome c." J.Mol.Biol.in press. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishii,I.,Kataoka,M.,Tokunaga,F. & Goto,Y.: "Cold-Denaturation of the Molten Globule States of Apomyoglobin and a Profile for Protein Folding." Biochemistry. in press. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Goto,Y. & Fink,A.L.: "Acid-induced Folding of Heme Proteins." Methods in Enzymology:Hemoglobin,Part B. in press. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Fink,A.L.,Calciano,L.J.Goto,Y.,Nishimura,M. & Swedberg,S.A.: "Characterization of the Stable,Acid-induced,Molten Globule-like State of Staphylococcal Nuclease." Protein Science. 2. 1155-1160 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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