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Sci Rep. 2017 Mar 16;7:44558. doi: 10.1038/srep44558.

S-nitrosylation of UCHL1 induces its structural instability and promotes α-synuclein aggregation.

Author information

1
Functional Proteomics Laboratory, Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.
2
Manipal University, Manipal, Karnataka, 576104, India.
3
Transcription Regulation Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, 110067, India.
4
Molecular Neuroscience Laboratory, National Brain Research Centre (NBRC), Manesar, Gurgaon, 122051, India.
5
Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.

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.

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