Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
ISSN: 0974-276X
Desmond Lau
Canada
Research Article
Design and Selection of IFI16-PAAD Mutants with Improved dsDNA Destabilization Properties
Author(s): Desmond Lau, Kush Dalal, Benjamin Hon and Frederic Pio
Desmond Lau, Kush Dalal, Benjamin Hon and Frederic Pio
The PAAD Death Domain is a 6-helix bundle domain that contains a disordered region in helix-3. This domain can fold by a two-state mechanism, has low stability and can undergo different partially folded conformations. To identify specific amino acids responsible for these structural features we focus our study on the PAAD domain of IFI16, a protein sensor that recognizes viral nucleic acids and triggers the (Interleukin-β) inflammatory response in response to infection. IFI16-PAAD was randomly mutated using GFP directed evolution and the resulting mutants with increased secondary structure and stability were identified by circular dichroism and tested for nucleic acid binding. Several IFI16-PAAD-GFP fusion mutants that contained I46N/S substitutions translated into improved secondary structure and stability and a direct correlation was observed between secondary structure/stabili.. View More»
DOI:
10.4172/jpb.1000414