This title appears in the Scientific Report :
2020
Please use the identifier:
http://dx.doi.org/10.1038/s42003-020-1085-z in citations.
Please use the identifier: http://hdl.handle.net/2128/25569 in citations.
Clustering of human prion protein and α-synuclein oligomers requires the prion protein N-terminus
Clustering of human prion protein and α-synuclein oligomers requires the prion protein N-terminus
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...
Saved in:
Personal Name(s): | Rösener, Nadine |
---|---|
Gremer, Lothar / Wördehoff, Michael M. / Kupreichyk, Tatsiana / Etzkorn, Manuel / Neudecker, Philipp / Hoyer, Wolfgang (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 |
Published in: | Communications biology, 3 (2020) 1, S. 365 |
Imprint: |
London
Springer Nature
2020
|
PubMed ID: |
32647130 |
DOI: |
10.1038/s42003-020-1085-z |
Document Type: |
Journal Article |
Research Program: |
Physical Basis of Diseases |
Link: |
Get full text Get full text OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/25569 in citations.
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. |