Locally Disordered Conformer of the Hamster Prion Protein:  A Crucial Intermediate to PrP<sup>Sc</sup>?

DOI HANDLE Web Site PubMed 6 Citations
  • Kazuo Kuwata
    Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan, Department of Molecular Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan, and Departments of Neurology, Biochemistry and Biophysics, and Pharmaceutical Chemistry and Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94946-0446
  • Hua Li
    Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan, Department of Molecular Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan, and Departments of Neurology, Biochemistry and Biophysics, and Pharmaceutical Chemistry and Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94946-0446
  • Hiroaki Yamada
    Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan, Department of Molecular Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan, and Departments of Neurology, Biochemistry and Biophysics, and Pharmaceutical Chemistry and Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94946-0446
  • Giuseppe Legname
    Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan, Department of Molecular Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan, and Departments of Neurology, Biochemistry and Biophysics, and Pharmaceutical Chemistry and Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94946-0446
  • Stanley B. Prusiner
    Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan, Department of Molecular Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan, and Departments of Neurology, Biochemistry and Biophysics, and Pharmaceutical Chemistry and Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94946-0446
  • Kazuyuki Akasaka
    Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan, Department of Molecular Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan, and Departments of Neurology, Biochemistry and Biophysics, and Pharmaceutical Chemistry and Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94946-0446
  • Thomas L. James
    Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan, Department of Molecular Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan, and Departments of Neurology, Biochemistry and Biophysics, and Pharmaceutical Chemistry and Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94946-0446

Description

A crucial step for transformation of the normal cellular isoform of the prion protein (PrP(C)) to the infectious prion protein (PrP(Sc)) is thought to entail a previously uncharacterized intermediate conformer, PrP*, which interacts with a template PrP(Sc) molecule in the conversion process. By carrying out (15)N-(1)H two-dimensional NMR measurements under variable pressure on Syrian hamster prion protein rPrP(90-231), we found a metastable conformer of PrP(C) coexisting at a population of approximately 1% at pH 5.2 and 30 degrees C, in which helices B and C are preferentially disordered. While the identity is still unproven, this observed metastable conformer is most logically PrP* or a closely related precursor. The structural characteristics of this metastable conformer are consistent with available immunological and pathological information about the prion protein.

Journal

  • Biochemistry

    Biochemistry 41 (41), 12277-12283, 2002-09-18

    American Chemical Society (ACS)

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