Single‐Molecule FRET Reveals Structural Heterogeneity of SDS‐Bound α‐Synuclein

Abstract

SDS-concentration-dependent alpha-synuclein structure: Upon interaction with SDS, alpha Syn folds into a structure with two antiparallel alpha-helices. We show from single-molecule FRET that alpha Synn adopts this conformation in an all-or-none fashion below the SDS critical micelle concentration. Population of the folded species is directly coupled to an increase in alpha-helix content; this suggests that the entire N terminus is involved in the transaction.

Segmental Conformational Disorder and Dynamics in the Intrinsically Disordered Protein α-Synuclein and Its Chain Length Dependence

“…61,62 Single-molecule FRET experiments also yield wide single-component intramolecular distance distributions with rapid fluctuations. 61,63,64 These experiments support the use of the diffusion model in the analysis of our results. With current probes and instrumentation, the single-molecule FRET experiments are more powerful for long intramolecular distance determination, and the larger probes (compared to those used in the present study) are more sensitive to intramolecular interactions.…”

SDS-Induced Fibrillation of α-Synuclein: An Alternative Fibrillation Pathway

“…The natively unfolded nature of αSN gives rise to a multistate folding when titrated with SDS, going from random coil to different α-helical folded states around the critical micelle concentration (CMC) of SDS. [29][30][31][32] It can take days to months for fibrillation to occur. 7,33,34 However, addition of negatively charged polymers or colloids such as heparin, heparin sulfate, dextran sulfate, and anionic surfactants accelerates the kinetics of αSN fibrillation.…”

Membrane Binding of Parkinson's Protein Alpha-Synuclein: Effect of Phosphorylation at Positions 87 and 129 by the S to D Mutation Approach

“…All aSm utants were expressed in Escherichia coli strain BL21(DE3) using the pT7-7 expression plasmid and puri- fied in the presence of 1mMD TT,a sp reviously reported [51,52] Serine-87 is substituted either by Alanine (S87A, represents phosphorylation-inactive form) or by Aspartate (S87D, represents phosphomimic form). Forl abelling, ac ysteine mutation was introduced at the desired residues.…”