Title
Aromaticity at position 39 in α-synuclein: A modulator of amyloid fibril assembly and membrane-bound conformations
Author
Fiamma A. Buratti, Nicola Boeffinger, Hugo A. Garro, Jesica S. Flores, Francisco J. Hita, Phelippe do Carmo Gonçalves, Federico dos Reis Copello, Leonardo Lizarraga, Giulia Rossetti, Paolo Carloni, Markus Zweckstetter, Tiago F. Outeiro, Stefan Eimer, Christian Griesinger, Claudio O. Fernández
Year
2022
Journal
Protein Science
Abstract
Recent studies revealed that molecular events related with the physiology and pathology of αS might be regulated by specific sequence motifs in the primary sequence of αS. The importance of individual residues in these motifs remains an important open avenue of investigation. In this work, we have addressed the structural details related to the amyloid fibril assembly and lipid-binding features of αS through the design of site-directed mutants at position 39 of the protein and their study by in vitro and in vivo assays. We demonstrated that aromaticity at position 39 of αS primary sequence influences strongly the aggregation properties and the membrane-bound conformations of the protein, molecular features that might have important repercussions for the function and dysfunction of αS. Considering that aggregation and membrane damage is an important driver of cellular toxicity in amyloid diseases, future work is needed to link our findings with studies based on toxicity and neuronal cell death.
Full Article
Instrument
J-1500
Keywords
α-synuclein, amyloid, protein, aggregation