bi400999d_si_001.pdf (3.09 MB)
The Parkinson’s Disease-Associated H50Q Mutation Accelerates α‑Synuclein Aggregation in Vitro
journal contribution
posted on 2013-10-08, 00:00 authored by Dhiman Ghosh, Mrityunjoy Mondal, Ganesh
M. Mohite, Pradeep
K. Singh, Priyatosh Ranjan, A. Anoop, Saikat Ghosh, Narendra Nath Jha, Ashutosh Kumar, Samir K. Majiα-Synuclein (α-Syn) aggregation
is directly linked
with Parkinson’s disease (PD) pathogenesis. Here, we analyzed
the aggregation of newly discovered α-Syn missense mutant H50Q in vitro and found that this mutation significantly accelerates
the aggregation and amyloid formation of α-Syn. This mutation,
however, did not alter the overall secondary structure as suggested
by two-dimensional nuclear magnetic resonance and circular dichroism
spectroscopy. The initial oligomerization study by cross-linking and
chromatographic techniques suggested that this mutant oligomerizes
to an extent similar to that of the wild-type α-Syn protein.
Understanding the aggregation mechanism of this H50Q mutant may help
to establish the aggregation and phenotypic relationship of this novel
mutant in PD.