title: S-nitrosylation of UCHL1 induces its structural instability and promotes α-synuclein aggregation.
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.
authors.affiliation: Functional Proteomics Laboratory, Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.|Manipal University, Manipal, Karnataka, 576104, India.
authors.forename: Roshan
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Functional Proteomics Laboratory, Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Jangir
authors.affiliation: Transcription Regulation Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Verma
authors.affiliation: Molecular Neuroscience Laboratory, National Brain Research Centre (NBRC), Manesar, Gurgaon, 122051, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Shekhar
authors.affiliation: Functional Proteomics Laboratory, Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.|Manipal University, Manipal, Karnataka, 576104, India.
authors.forename: Pranita
authors.initials: P
authors.lastname: Hanpude
authors.affiliation: Functional Proteomics Laboratory, Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.|Manipal University, Manipal, Karnataka, 576104, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Functional Proteomics Laboratory, Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.
authors.forename: Raniki
authors.initials: R
authors.lastname: Kumari
authors.affiliation: Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.
authors.forename: Nirpendra
authors.initials: N
authors.lastname: Singh
authors.affiliation: Transcription Regulation Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Neel
authors.initials: N
authors.lastname: Sarovar Bhavesh
authors.affiliation: Molecular Neuroscience Laboratory, National Brain Research Centre (NBRC), Manesar, Gurgaon, 122051, India.
authors.forename: Nihar
authors.initials: N
authors.lastname: Ranjan Jana
authors.affiliation: Functional Proteomics Laboratory, Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, 121001, India.
authors.forename: Tushar
authors.initials: T
authors.lastname: Kanti Maiti
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000235:genetics*; D012402:Rotenone / Q000633:toxicity; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000235:genetics*; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics
chemical_list: C482860:UCHL1 protein, human; D051844:alpha-Synuclein; D012402:Rotenone; D043222:Ubiquitin Thiolesterase