The Parkinson’s Disease-Associated H50Q Mutation
Accelerates α‑Synuclein Aggregation <i>in Vitro</i>
Dhiman Ghosh
Mrityunjoy Mondal
Ganesh
M. Mohite
Pradeep
K. Singh
Priyatosh Ranjan
A. Anoop
Saikat Ghosh
Narendra Nath Jha
Ashutosh Kumar
Samir K. Maji
10.1021/bi400999d.s001
https://acs.figshare.com/articles/journal_contribution/The_Parkinson_s_Disease_Associated_H50Q_Mutation_Accelerates_Synuclein_Aggregation_i_in_Vitro_i_/2368417
α-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 <i>in vitro</i> 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.
2013-10-08 00:00:00
H 50Q
Syn
mutation
PD
aggregation
Parkinson