| Autor: |
Leitão, André D. G., Rudolffi-Soto, Paulina, Chappard, Alexandre, Bhumkar, Akshay, Lau, Derrick, Hunter, Dominic J. B., Gambin, Yann, Sierecki, Emma |
| Předmět: |
|
| Zdroj: |
Communications Biology; 9/23/2021, Vol. 4 Issue 1, p1-16, 16p |
| Abstrakt: |
The aggregation of alpha-synuclein (α-SYN) follows a cascade of oligomeric, prefibrillar and fibrillar forms, culminating in the formation of Lewy Bodies (LB), the pathological hallmarks of Parkinson's Disease. Although LB contain over 70 proteins, the potential for interactions along the aggregation pathway of α-SYN is unknown. Here we propose a map of interactions of 65 proteins against different species of α-SYN. We measured binding to monomeric α-SYN using AlphaScreen, a sensitive nano-bead luminescence assay for detection of protein interactions. To access oligomeric species, we used the pathological mutants of α-SYN (A30P, G51D and A53T) which form oligomers with distinct properties. Finally, we generated amyloid fibrils from recombinant α-SYN. Binding to oligomers and fibrils was measured by two-color coincidence detection (TCCD) on a single molecule spectroscopy setup. Overall, we demonstrate that LB components are recruited to specific steps in the aggregation of α-SYN, uncovering future targets to modulate aggregation in synucleinopathies. To better understand the specific cascade of protein interactions that lead to the pathological aggregation of α-synuclein (wild-type and mutant forms), Leitão et al. present a method to measure interactions of monomeric, oligomeric, and fibrillar forms of α-syn with 65 proteins that were previously shown to be components of Lewy bodies. This approach is useful to understand the sequence of protein-binding events that lead to α-syn aggregation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
