Broken helix in vesicle and micelle-bound alpha-synuclein: insights from site-directed spin labeling-EPR experiments and MD simulations.
The region 35-43 of human alpha-Synuclein bound to small unilamellar lipid vesicles and to sodium dodecyl sulfate micelles has been investigated by site-directed spin labeling and electron paramagnetic resonance spectroscopy. The distance distributions obtained from spectral fitting have been analyzed on the basis of the allowed rotamers of the spin-label side-chain. Very similar results have been obtained in the two environments: an unbroken helical structure of the investigated region can be ruled out. The distance distributions are rather compatible with the presence of conformational disorder, in agreement with previous findings for micelle-bound alpha-Synuclein. The propensity for helix breaking is confirmed by molecular dynamics simulations.
Bortolus
Marco
M
Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo, 1, 35131 Padova, Italy.
Tombolato
Fabio
F
Tessari
Isabella
I
Bisaglia
Marco
M
Mammi
Stefano
S
Bubacco
Luigi
L
Ferrarini
Alberta
A
Maniero
Anna Lisa
AL
D000595:Amino Acid Sequence; D003198:Computer Simulation; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013113:Spin Labels; D051844:alpha-Synuclein / Q000737:chemistry*
D008051:Lipid Bilayers; D008823:Micelles; D010713:Phosphatidylcholines; D013113:Spin Labels; D051844:alpha-Synuclein; D012967:Sodium Dodecyl Sulfate; C028694:1-palmitoyl-2-oleoylphosphatidylcholine