title: Functional regulation of PVBV Nuclear Inclusion protein-a protease activity upon interaction with Viral Protein genome-linked and phosphorylation.
abstract: Regulation of NIa-Pro is crucial for polyprotein processing and hence, for successful infection of potyviruses. We have examined two novel mechanisms that could regulate NIa-Pro activity. Firstly, the influence of VPg domain on the proteolytic activity of NIa-Pro was investigated. It was shown that the turnover number of the protease increases when these two domains interact (cis: two-fold; trans: seven-fold) with each other. Secondly, the protease activity of NIa-Pro could also be modulated by phosphorylation at Ser129. A mutation of this residue either to aspartate (phosphorylation-mimic) or alanine (phosphorylation-deficient) drastically reduces the protease activity. Based on these observations and molecular modeling studies, we propose that interaction with VPg as well as phosphorylation of Ser129 could relay a signal through Trp143 present at the protein surface to the active site pocket by subtle conformational changes, thus modulating protease activity of NIa-Pro.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore-560012, India.
authors.forename: C
authors.initials: C
authors.lastname: Mathur
authors.forename: V K
authors.initials: VK
authors.lastname: Jimsheena
authors.forename: S
authors.initials: S
authors.lastname: Banerjee
authors.forename: K
authors.initials: K
authors.lastname: Makinen
authors.forename: L R
authors.initials: LR
authors.lastname: Gowda
authors.forename: H S
authors.initials: HS
authors.lastname: Savithri
mesh_terms: D001483:Base Sequence; D002855:Chromatography, Thin Layer; D002942:Circular Dichroism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D016679:Genome, Viral; D009154:Mutation; D010766:Phosphorylation; D017800:Potyvirus / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins; D010450:Endopeptidases; C059992:nuclear inclusion protein a, mosaic viruses