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The N‐terminus of α‐synuclein is essential for both monomeric and oligomeric interactions with membranes
Author(s) -
Lorenzen Nikolai,
Lemminger Lasse,
Pedersen Jannik Nedergaard,
Nielsen Søren Bang,
Otzen Daniel Erik
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.12.015
Subject(s) - oligomer , monomer , membrane , chemistry , biophysics , fibril , folding (dsp implementation) , protein folding , cytotoxicity , amyloid (mycology) , biochemistry , polymer chemistry , biology , in vitro , polymer , organic chemistry , inorganic chemistry , electrical engineering , engineering
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.