Kumar, Roshan and Jangir, Deepak K. and Verma, Garima and Shekhar, Shashi and Hanpude, Pranita and Kumar, Sanjay and Kumari, Raniki and Singh, Nirpendra and Sarovar Bhavesh, Neel and Ranjan Jana, Nihar and Kanti Maiti, Tushar (2017) S-nitrosylation of UCHL1 induces its structural instability and promotes α-synuclein aggregation. Scientific Reports, 7. p. 44558. ISSN 2045-2322

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Abstract

Ubiquitin C-terminal Hydrolase-1 (UCHL1) is a deubiquitinating enzyme, which plays a key role in Parkinson’s disease (PD). It is one of the most important proteins, which constitute Lewy body in PD patient. However, how this well folded highly soluble protein presents in this proteinaceous aggregate is still unclear. We report here that UCHL1 undergoes S-nitrosylation in vitro and rotenone induced PD mouse model. The preferential nitrosylation in the Cys 90, Cys 152 and Cys 220 has been observed which alters the catalytic activity and structural stability. We show here that nitrosylation induces structural instability and produces amorphous aggregate, which provides a nucleation to the native α-synuclein for faster aggregation. Our findings provide a new link between UCHL1-nitrosylation and PD pathology.

Item Type:	Article
Subjects:	Biochemical and Biophysical Sciences
Depositing User:	Dr Vengadesan Krishnan
Date Deposited:	13 Oct 2017 14:28
Last Modified:	30 Aug 2018 11:55
URI:	http://rcb.sciencecentral.in/id/eprint/50

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