TY  - JOUR
AU  - Dürnberger, Yvonne
AU  - Liu, Shu
AU  - Riemschoß, Katrin
AU  - Paulsen, Lydia
AU  - Bester, Romina
AU  - Kuhn, Peer-Hendrik
AU  - Schölling, Manuel
AU  - Lichtenthaler, Stefan F
AU  - Vorberg, Ina
TI  - Prion Replication in the Mammalian Cytosol: Functional Regions within a Prion Domain Driving Induction, Propagation, and Inheritance.
JO  - Molecular and cellular biology
VL  - 38
IS  - 15
SN  - 0270-7306
CY  - Washington, DC
PB  - Soc.
M1  - DZNE-2020-06408
SP  - e00111-18/mcb/38/15/e00111-18.atom
PY  - 2018
AB  - 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.
KW  - Amino Acid Sequence
KW  - Animals
KW  - Binding Sites
KW  - Cell Line
KW  - Cytosol: metabolism
KW  - Mice
KW  - Models, Molecular
KW  - Mutation
KW  - Peptide Termination Factors: biosynthesis
KW  - Peptide Termination Factors: chemistry
KW  - Peptide Termination Factors: genetics
KW  - Prion Proteins: biosynthesis
KW  - Prion Proteins: chemistry
KW  - Prion Proteins: genetics
KW  - Prions: biosynthesis
KW  - Prions: chemistry
KW  - Prions: genetics
KW  - Protein Aggregates: genetics
KW  - Protein Aggregation, Pathological: genetics
KW  - Protein Aggregation, Pathological: metabolism
KW  - Protein Domains
KW  - Protein Folding
KW  - Recombinant Proteins: biosynthesis
KW  - Recombinant Proteins: chemistry
KW  - Recombinant Proteins: genetics
KW  - Saccharomyces cerevisiae Proteins: biosynthesis
KW  - Saccharomyces cerevisiae Proteins: chemistry
KW  - Saccharomyces cerevisiae Proteins: genetics
KW  - Sequence Deletion
KW  - Peptide Termination Factors (NLM Chemicals)
KW  - Prion Proteins (NLM Chemicals)
KW  - Prions (NLM Chemicals)
KW  - Protein Aggregates (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - SUP35 protein, S cerevisiae (NLM Chemicals)
KW  - Saccharomyces cerevisiae Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29784771
C2  - pmc:PMC6048315
DO  - DOI:10.1128/MCB.00111-18
UR  - https://pub.dzne.de/record/140086
ER  -