The Mechanism of Prion Inhibition by HET-S
| Autor: | Frédérique Ness, Jason Greenwald, Marie-Lise Maddelein, Roland Riek, Carolin Buhtz, Senyon Choe, Dominik Leitz, Witek Kwiatkowski, Sven J. Saupe, Christiane Ritter, Alice Soragni, Sandra Cescau |
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| Přispěvatelé: | Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Helmholtz Centre for Infection Research (HZI), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Bordeaux (UB), UCLA/DOE Institute for Genomics and Proteomics, University of California [Los Angeles] (UCLA), University of California-University of California, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular animal structures Prions Protein Conformation [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Molecular Sequence Data [SDV.CAN]Life Sciences [q-bio]/Cancer macromolecular substances Biology Crystallography X-Ray Fibril Article Fungal Proteins 03 medical and health sciences 0302 clinical medicine Protein structure In vivo Amino Acid Sequence [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Peptide sequence Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences Fungal protein [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Protein Stability [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences Protein multimerization In vitro Protein Structure Tertiary Solutions Biochemistry Mutation Biophysics [SDV.IB]Life Sciences [q-bio]/Bioengineering Trans-acting Protein Multimerization 030217 neurology & neurosurgery |
| Zdroj: | Molecular Cell Molecular Cell, Elsevier, 2010, 38 (6), pp.889-899. ⟨10.1016/j.molcel.2010.05.019⟩ Scopus-Elsevier |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2010.05.019⟩ |
| Popis: | HET-S (97% identical to HET-s) has an N-terminal globular domain that exerts a prion-inhibitory effect in cis on its own prion-forming domain (PFD) and in trans on HET-s prion propagation. We show that HET-S fails to form fibrils in vitro and that it inhibits HET-s PFD fibrillization in trans. In vivo analyses indicate that beta-structuring of the HET-S PFD is required for HET-S activity. The crystal structures of the globular domains of HET-s and HET-S are highly similar, comprising a helical fold, while NMR-based characterizations revealed no differences in the conformations of the PFDs. We conclude that prion inhibition is not encoded by structure but rather in stability and oligomerization properties: when HET-S forms a prion seed or is incorporated into a HET-s fibril via its PFD, the beta-structuring in this domain induces a change in its globular domain, generating a molecular species that is incompetent for fibril growth. |
| Databáze: | OpenAIRE |
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