Order–disorder skewness in alpha-synuclein: a key mechanism to recognize membrane curvature

Currently, membrane curvature is understood as an active mechanism to control cells spatial organization and activity. Protein processes involved in sensing and generating curvature are therefore of major interest. In this work, we have studied α-synuclein interactions with a model lipid bilayer, inducing curvature in a controlled manner and describing protein responses at molecular level. We show that the intrinsically disordered region of α-synuclein binds to the bilayer as an acknowledgment to the induced curvature, a mechanism used by the interacting protein-membrane assembly to relieve free energy. We have calculated free energies for bending the bilayer with α-synuclein adsorbed on the surface and we have established the crucial role of the intrinsically disordered region, suggesting that a dynamic order/disorder interplay takes place as the bilayer reorganizes to bend.