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@ARTICLE{Drnberger:140086,
author = {Dürnberger, Yvonne and Liu, Shu and Riemschoß, Katrin and
Paulsen, Lydia and Bester, Romina and Kuhn, Peer-Hendrik and
Schölling, Manuel and Lichtenthaler, Stefan F and Vorberg,
Ina},
title = {{P}rion {R}eplication in the {M}ammalian {C}ytosol:
{F}unctional {R}egions within a {P}rion {D}omain {D}riving
{I}nduction, {P}ropagation, and {I}nheritance.},
journal = {Molecular and cellular biology},
volume = {38},
number = {15},
issn = {0270-7306},
address = {Washington, DC},
publisher = {Soc.},
reportid = {DZNE-2020-06408},
pages = {e00111-18/mcb/38/15/e00111-18.atom},
year = {2018},
abstract = {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.},
keywords = {Amino Acid Sequence / Animals / Binding Sites / Cell Line /
Cytosol: metabolism / Mice / Models, Molecular / Mutation /
Peptide Termination Factors: biosynthesis / Peptide
Termination Factors: chemistry / Peptide Termination
Factors: genetics / Prion Proteins: biosynthesis / Prion
Proteins: chemistry / Prion Proteins: genetics / Prions:
biosynthesis / Prions: chemistry / Prions: genetics /
Protein Aggregates: genetics / Protein Aggregation,
Pathological: genetics / Protein Aggregation, Pathological:
metabolism / Protein Domains / Protein Folding / Recombinant
Proteins: biosynthesis / Recombinant Proteins: chemistry /
Recombinant Proteins: genetics / Saccharomyces cerevisiae
Proteins: biosynthesis / Saccharomyces cerevisiae Proteins:
chemistry / Saccharomyces cerevisiae Proteins: genetics /
Sequence Deletion / Peptide Termination Factors (NLM
Chemicals) / Prion Proteins (NLM Chemicals) / Prions (NLM
Chemicals) / Protein Aggregates (NLM Chemicals) /
Recombinant Proteins (NLM Chemicals) / SUP35 protein, S
cerevisiae (NLM Chemicals) / Saccharomyces cerevisiae
Proteins (NLM Chemicals)},
cin = {AG Vorberg / AG Lichtenthaler / IDAF},
ddc = {570},
cid = {I:(DE-2719)1013004 / I:(DE-2719)1110006 /
I:(DE-2719)1040200},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
experiment = {EXP:(DE-2719)IDAF-20190308},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29784771},
pmc = {pmc:PMC6048315},
doi = {10.1128/MCB.00111-18},
url = {https://pub.dzne.de/record/140086},
}