Biophysical Characterization of Lithostathine
Autor: | Alain Vazi, Laure Duplan, Bernard Michel, Henri Bouteille, Jean-Paul Bernard, Jean-Pierre Le Caer, Yvon Berland, R. Michel, Stéphane Veesler, Claire Cerini, Cyrille Garnier, Jean-Michel Verdier, Vincent Peyrot, Patricia Dupuy |
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Přispěvatelé: | Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interaction entre Systèmes Protéiques et Différenciation dans la Cellule Tumorale (ISPDCT), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie et diversité cellulaire (NDC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), VEGATEC, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 1999 |
Předmět: |
0303 health sciences
medicine.diagnostic_test Chemistry Lithostathine Proteolysis macromolecular substances Cell Biology Fibril Cleavage (embryo) Trypsin Biochemistry 3. Good health 03 medical and health sciences 0302 clinical medicine Calcium-binding protein medicine [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci] Peptide bond Ultracentrifuge Molecular Biology 030217 neurology & neurosurgery ComputingMilieux_MISCELLANEOUS 030304 developmental biology medicine.drug |
Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, 1999, 274 (32), pp.22266-22274. ⟨10.1074/jbc.274.32.22266⟩ Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1999, 274 (32), pp.22266-22274. ⟨10.1074/jbc.274.32.22266⟩ |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.32.22266⟩ |
Popis: | Lithostathine is a calcium carbonate crystal habit modifier. It is found precipitated under the form of fibrils in chronic calcifying pancreatitis or Alzheimer's disease. In order to gain better insight into the nature and the formation of fibrils, we have expressed and purified recombinant lithostathine. Analytical ultracentrifugation and quasi-elastic light scattering techniques were used to demonstrate that lithostathine remains essentially monomeric at acidic pH while it aggregates at physiological pH. Analysis of these aggregates by electron microscopy showed an apparently unorganized structure of numerous monomers which tend to precipitate forming regular unbranched fibrils. Aggregated forms seem to occur prior to the apparition of fibrils. In addition, we have demonstrated that these fibrils resulted from a proteolysis mechanism due to a specific cleavage of the Arg(11)-Ile(12) peptide bond. It is deduced that the NH(2)-terminal undecapeptide of lithostathine normally impedes fiber formation but not aggregation. A theoretical model explaining the formation of amyloid plaques in neurodegenerative diseases or stones in lithiasis starting from lithostathine is described. Therefore we propose that lithostathine, whose major function is unknown, defines a new class of molecules which is activated by proteolysis and is not involved in cytoskeleton nor intermediate filament functions. |
Databáze: | OpenAIRE |
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