Effect of C-terminal truncations on the aggregation propensity of A53E, a familial mutant of α-Synuclein: An Insilico Study

Airy Sanjeev, Venkata Satish Kumar Mattaparthi


α-Synuclein, an intrinsically disordered protein, is well known for its role on the onset of Parkinson’s Disease (PD), a neurodegenerative disorder. In α-synuclein, several mutations have been known to cause genetic forms of PD. Recently a new familial mutant, A53E of α-synuclein was discovered in a family and found to accelerate the α-synuclein gene, SNCA. But the molecular details about the A53E α-synuclein aggregation were not well studied. It has been recently suggested that two C-terminally truncated α-synuclein (αS C-X): 120 and 123, along with the A53E mutation would cause a more aggressive pathology and an increase in aggregation. So here we demonstrate the effect of C-terminal truncations along with A53E mutation on the aggregation propensity of α-synuclein by comparing the conformational dynamics of A53E full length protein and its C-terminal truncations using molecular dynamics simulation methods. In A53E full length protein we observed stability to be more and also hydrophobic surface (NAC (non-amyloid β component) region), number of molecular interactions and interface area between monomeric units to be relatively less than αS C-X. Our findings in this study suggest that more the residues removed from the C-terminal along with A53E mutation have significant effect on the aggregation propensity of α-synuclein.


Parkinson’s disease; amyloid; truncation; fibrillation; molecular dynamics

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