Clustering of human prion protein and α-synuclein oligomers requires the prion protein N-terminus.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
09 07 2020
09 07 2020
Historique:
received:
28
11
2019
accepted:
18
06
2020
entrez:
11
7
2020
pubmed:
11
7
2020
medline:
16
6
2021
Statut:
epublish
Résumé
The interaction of prion protein (PrP) and α-synuclein (αSyn) oligomers causes synaptic impairment that might trigger Parkinson's disease and other synucleinopathies. Here, we report that αSyn oligomers (αSynO) cluster with human PrP (huPrP) into micron-sized condensates. Multivalency of αSyn within oligomers is required for condensation, since clustering with huPrP is not observed for monomeric αSyn. The stoichiometry of the heteroassemblies is well defined with an αSyn:huPrP molar ratio of about 1:1. The αSynO-huPrP interaction is of high affinity, signified by slow dissociation. The huPrP region responsible for condensation of αSynO, residues 95-111 in the intrinsically disordered N-terminus, corresponds to the region required for αSynO-mediated cognitive impairment. HuPrP, moreover, achieves co-clustering of αSynO and Alzheimer's disease-associated amyloid-β oligomers, providing a case of a cross-interaction of two amyloidogenic proteins through an interlinking intrinsically disordered protein region. The results suggest that αSynO-mediated condensation of huPrP is involved in the pathogenesis of synucleinopathies.
Identifiants
pubmed: 32647130
doi: 10.1038/s42003-020-1085-z
pii: 10.1038/s42003-020-1085-z
pmc: PMC7347944
doi:
Substances chimiques
Amyloid beta-Peptides
0
Prion Proteins
0
SNCA protein, human
0
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
365Subventions
Organisme : European Research Council
ID : 726368
Pays : International
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