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Molecular Details of α-Synuclein Membrane Association Revealed by Neutrons and Photons



Zhiping Jiang, Sara K. Hess, Frank Heinrich, Jennifer C. Lee


α-Synuclein (α-syn) is an abundant neuronal protein associated with Parkinson's disease that is disordered in solution, but exists in equilibrium between a bent- and elongated-helix on negatively charged membranes. Here, neutron reflectometry (NR) and fluorescence spectroscopy were employed to uncover molecular details of the interaction between α-syn and two anionic lipids, phosphatidic acid (PA) and phosphatidylserine (PS). NR data show that α-syn penetrates either PA- or PS-containing sparsely tethered bilayer lipid membranes to a similar depth ( 11A from bilayer center) even though α-syn binds more tightly to PA in mildly acidic (pH 5.5) solutions. Consistent penetration depths on the residue level were obtained using three single-Trp variants (F4W, Y39W, and F94W) and, in particular, the spectroscopic properties of W39 were found to be sensitive to the chemical nature of the membrane surface. Our data indicate the coexistence of multiple membrane-bound conformations including the bent helix; however, we revised the existing elongated helical model with an additional break at residues 88-91 to corroborate the observation that W94 penetrates the bilayer, whereas, previously, there was only one deviation from a canonical helix at residues 53-56.
Journal of Physical Chemistry B


circular dichroism, fluorescence, neutron reflectometry, protein-lipid interaction, tryptophan


Jiang, Z. , Hess, S. , Heinrich, F. and Lee, J. (2015), Molecular Details of α-Synuclein Membrane Association Revealed by Neutrons and Photons, Journal of Physical Chemistry B, [online], (Accessed June 19, 2024)


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Created March 18, 2015, Updated October 12, 2021