A protein-chameleon:: Conformational plasticity of α-synuclein, a disordered protein involved in neurodegenerative disorders

Under the physiological conditions in vitro, a-synuclein, a conservative presynaptic protein, the aggregation and fibrillation of which is assumed to be involved into the pathogenesis of Parkinson's disease and several other neurodegenerative disorders, known as synucle-inopathies, is characterized by the lack of rigid well-defined structure; i.e., it belongs to the class of intrinsically unstructured proteins. Intriguingly, a-synuclein is characterized by a remarkable conformational plasticity, adopting a series of different conformations depending on the environment. For example, this protein may either stay substantially unfolded, or adopt an amyloidogenic partially folded conformation, or fold into a-helical or P-structural species, both monomeric and oligomeric. Furthermore, it might form several morphologically different types of aggregates, including oligomers (spheres or doughnuts), amorphous aggregates, and or amyloid-like fibrils. The peculiarities of this astonishing conformational behavior are analyzed to shed light on structural plasticity of this protein-chameleon.