Prion Replication in the Mammalian Cytosol: Functional Regions within a Prion Domain Driving Induction, Propagation, and Inheritance
| Autor: | Romina Bester, Peer-Hendrik Kuhn, Katrin Riemschoss, Ina Vorberg, Yvonne Duernberger, Shu Liu, Manuel Schölling, Lydia Paulsen, Stefan F. Lichtenthaler |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Folding animal diseases chemistry [Recombinant Proteins] biosynthesis [Recombinant Proteins] chemistry [Prion Proteins] Mice Cytosol biosynthesis [Saccharomyces cerevisiae Proteins] protein misfolding Sequence Deletion prion-like Neurodegeneration biosynthesis [Peptide Termination Factors] Inheritance (genetic algorithm) neurodegeneration amyloid chemistry [Saccharomyces cerevisiae Proteins] chemistry [Peptide Termination Factors] Recombinant Proteins Cell biology ddc genetics [Recombinant Proteins] biosynthesis [Prions] Protein folding Research Article Peptide Termination Factors Saccharomyces cerevisiae Proteins Amyloid Prions Saccharomyces cerevisiae Biology Protein Aggregation Pathological Prion Proteins Cell Line 03 medical and health sciences Protein Aggregates metabolism [Protein Aggregation Pathological] Protein Domains ddc:570 medicine Animals genetics [Protein Aggregation Pathological] Amino Acid Sequence Molecular Biology genetics [Saccharomyces cerevisiae Proteins] Binding Sites genetics [Prions] Cell Biology chemistry [Prions] medicine.disease biology.organism_classification Yeast Fungal prion nervous system diseases 030104 developmental biology biosynthesis [Prion Proteins] Mutation genetics [Peptide Termination Factors] metabolism [Cytosol] genetics [Prion Proteins] SUP35 protein S cerevisiae genetics [Protein Aggregates] |
| Zdroj: | Molecular and cellular biology 38(15), e00111-18/mcb/38/15/e00111-18.atom (2018). doi:10.1128/MCB.00111-18 Molecular and Cellular Biology |
| DOI: | 10.1128/MCB.00111-18 |
| Popis: | Prions of lower eukaryotes are transmissible protein particles that propagate by converting homotypic soluble proteins into growing protein assemblies. Prion activity is conferred by so-called prion domains, regions of low complexity that are often enriched in glutamines and asparagines (Q/N). Prions of lower eukaryotes are transmissible protein particles that propagate by converting homotypic soluble proteins into growing protein assemblies. Prion activity is conferred by so-called prion domains, regions of low complexity that are often enriched in glutamines and asparagines (Q/N). The compositional similarity of fungal prion domains with intrinsically disordered domains found in many mammalian proteins raises the question of whether similar sequence elements can drive prion-like phenomena in mammals. Here, we define sequence features of the prototype Saccharomyces cerevisiae Sup35 prion domain that govern prion activities in mammalian cells by testing the ability of deletion mutants to assemble into self-perpetuating particles. Interestingly, the amino-terminal Q/N-rich tract crucially important for prion induction in yeast was dispensable for the prion life cycle in mammalian cells. Spontaneous and template-assisted prion induction, growth, and maintenance were preferentially driven by the carboxy-terminal region of the prion domain that contains a putative soft amyloid stretch recently proposed to act as a nucleation site for prion assembly. Our data demonstrate that preferred prion nucleation domains can differ between lower and higher eukaryotes, resulting in the formation of prions with strikingly different amyloid cores. |
| Databáze: | OpenAIRE |
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