A protein-chameleon: conformational plasticity of alpha-synuclein, a disordered protein involved in neurodegenerative disorders.
Under the physiological conditions in vitro, alpha-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 synucleinopathies, is characterized by the lack of rigid well-defined structure; i.e., it belongs to the class of intrinsically unstructured proteins. Intriguingly, alpha-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 alpha-helical or beta-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.
Uversky
Vladimir N
VN
Institute for Biological Instrumentation, Russian Academy of Sciences Pushchino, Moscow Region, Russia. uversky@hydrogen.ucsc.edu
D000438:Alcohols / Q000737:chemistry; D000818:Animals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008670:Metals / Q000737:chemistry; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D010575:Pesticides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D051843:Synucleins; D051844:alpha-Synuclein
D000438:Alcohols; D008670:Metals; D009419:Nerve Tissue Proteins; D010575:Pesticides; D011108:Polymers; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein