α-Synuclein (αS) is a 140 amino acid protein whose aggregation into amyloid fibrils in a subset of neuronal and glial cells lies behind the onset of a group of progressive and, ultimately, fatal neurodegenerative disorders, including Parkinson’s disease (PD), that are collectively referred to as synucleinopathies. A causative link between αS and disease is supported by the discoveries that multiplications and missense mutations in SNCA, the αS gene, cause dominantly-inherited familial forms of PD. The in vitro aggregation of αS displays a sigmoidal growth profile, suggesting that it follows a nucleation-polymerization mechanism, where soluble αS undergoes a nucleation process that produces oligomers able to grow through further monomer addition to form insoluble amyloid fibrils. Oligomeric forms of αS have been detected in the brains and other tissues of patients suffering from PD, and growing evidence suggests that they constitute the primary cytotoxic agents accounting for the gain-of-toxicity associated with αS aggregation, whereas both oligomers and fibrils would be responsible for pathology dissemination. Synuclein fibrils can function as scaffolds of many different compounds, as demonstrated by in vitro experiments. Here you can see how the synuclein fibrils are able to bind copper-porphyrin, as determined by cryoEM analysis (PDB code: 7YNF)

#molecularart ... #fibril ... #synuclein ... #scaffold ... #porphyrin ... #copper ... #surface ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint