DNA mimic proteins have a DNA-like negative charge distribution on their surface, and they function by occupying the DNA binding sites of DNA binding proteins to prevent these sites from being accessed by DNA. The divergent amino acid sequences of the DNA mimics make these proteins hard to predict. To date, only a few (less than 20) have been reported and functionally analyzed. Recently, we successfully identified four new DNA mimic proteins: ICP11, DMP19, DMP12 and SAUGI by using structural and proteomic approaches. ICP11 from white spot syndrome virus interacts with eukaryotic histone proteins and disrupts nucleosome assembly. Neisseria DMP19 and DMP12 interact with the Neisseria transcription factors NHTF and HU, respectively. Staphylococcus SAUGI inhibits the uracil-removing activity of S. aureus uracil DNA glycosylase (SAUDG). However, we have only determined the SAUGI/SAUDG complex structure in the four previous studies. Here, we aim to extend our knowledge of the interaction between DNA mimic proteins and their targets. We will try to determine and analyze the crystal structures of ICP11/histone, DMP12/HU protein, DMP19/NHTF, SAUGI/human UDG and SAUGI/viral UDG complexes. The interacting residues in these complexes will be further confirmed by using site-directed mutagenesis in conjunction with functional assays. We believe that the results of this work will greatly extend the understanding of DNA mimics in general, and may open up potential ways to novel applications for this novel class of proteins.
|Effective start/end date||8/1/15 → 7/31/16|