Format

Send to

Choose Destination
FEBS Lett. 2014 Jan 31;588(3):497-502. doi: 10.1016/j.febslet.2013.12.015. Epub 2013 Dec 25.

The N-terminus of α-synuclein is essential for both monomeric and oligomeric interactions with membranes.

Author information

1
Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
2
Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark. Electronic address: dao@inano.au.dk.

Abstract

The intrinsically disordered protein α-synuclein (αSN) is linked to Parkinson's Disease and forms both oligomeric species and amyloid fibrils. The N-terminal part of monomeric αSN interacts strongly with membranes and αSN cytotoxicity has been attributed to oligomers' ability to interact with and perturb membranes. We show that membrane folding of monomeric wt αSN and N-terminally truncated variants correlates with membrane permeabilization. Further, the first 11 N-terminal residues are crucial for monomers' and oligomers' interactions with and permeabilization of membranes. We attribute oligomer permeabilization both to cooperative electrostatic interactions through the N-terminus and interactions mediated by hydrophobic regions in the oligomer.

KEYWORDS:

1-anilinonaphthalene-8-sulfonate; A4F; ANS; CD; DLS; Membrane folding; Membrane interaction; Oligomer; PD; Parkinson’s Disease; Permeabilization; SDS; SEC; ThT; Toxicity; asymmetrical flow field-flow fractionation; circular dichroism; dynamic light scattering; size exclusion chromatography; sodium dodecyl sulfate; thioflavin T; α-synuclein; αSN

PMID:
24374342
DOI:
10.1016/j.febslet.2013.12.015
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center