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@ARTICLE{Chandramowlishwaran:139830,
author = {Chandramowlishwaran, Pavithra and Sun, Meng and Casey,
Kristin L and Romanyuk, Andrey V and Grizel, Anastasiya V
and Sopova, Julia V and Rubel, Aleksandr A and
Nussbaum-Krammer, Carmen and Vorberg, Ina M and Chernoff,
Yury O},
title = {{M}ammalian amyloidogenic proteins promote prion nucleation
in yeast.},
journal = {The journal of biological chemistry},
volume = {293},
number = {9},
issn = {0021-9258},
address = {Bethesda, Md.},
publisher = {Soc.60645},
reportid = {DZNE-2020-06152},
pages = {3436-3450},
year = {2018},
abstract = {Fibrous cross-β aggregates (amyloids) and their
transmissible forms (prions) cause diseases in mammals
(including humans) and control heritable traits in yeast.
Initial nucleation of a yeast prion by transiently
overproduced prion-forming protein or its (typically,
QN-rich) prion domain is efficient only in the presence of
another aggregated (in most cases, QN-rich) protein. Here,
we demonstrate that a fusion of the prion domain of yeast
protein Sup35 to some non-QN-rich mammalian proteins,
associated with amyloid diseases, promotes nucleation of
Sup35 prions in the absence of pre-existing aggregates. In
contrast, both a fusion of the Sup35 prion domain to a
multimeric non-amyloidogenic protein and the expression of a
mammalian amyloidogenic protein that is not fused to the
Sup35 prion domain failed to promote prion nucleation,
further indicating that physical linkage of a mammalian
amyloidogenic protein to the prion domain of a yeast protein
is required for the nucleation of a yeast prion. Biochemical
and cytological approaches confirmed the nucleation of
protein aggregates in the yeast cell. Sequence alterations
antagonizing or enhancing amyloidogenicity of human
amyloid-β (associated with Alzheimer's disease) and mouse
prion protein (associated with prion diseases),
respectively, antagonized or enhanced nucleation of a yeast
prion by these proteins. The yeast-based prion nucleation
assay, developed in our work, can be employed for mutational
dissection of amyloidogenic proteins. We anticipate that it
will aid in the identification of chemicals that influence
initial amyloid nucleation and in searching for new
amyloidogenic proteins in a variety of proteomes.},
keywords = {Amyloid: metabolism / Amyloid beta-Peptides: metabolism /
Humans / Peptide Fragments: metabolism / Peptide Termination
Factors: chemistry / Peptide Termination Factors: metabolism
/ Protein Aggregates / Protein Domains / Saccharomyces
cerevisiae Proteins: chemistry / Saccharomyces cerevisiae
Proteins: metabolism / Amyloid (NLM Chemicals) / Amyloid
beta-Peptides (NLM Chemicals) / Peptide Fragments (NLM
Chemicals) / Peptide Termination Factors (NLM Chemicals) /
Protein Aggregates (NLM Chemicals) / SUP35 protein, S
cerevisiae (NLM Chemicals) / Saccharomyces cerevisiae
Proteins (NLM Chemicals) / amyloid beta-protein (1-40) (NLM
Chemicals) / amyloid beta-protein (1-42) (NLM Chemicals)},
cin = {AG Vorberg},
ddc = {540},
cid = {I:(DE-2719)1013004},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29330303},
pmc = {pmc:PMC5836139},
doi = {10.1074/jbc.M117.809004},
url = {https://pub.dzne.de/record/139830},
}