Our research focuses on the structural biology of proteins involved in signal transduction (STATs, cytokines, hepatocyte growth factor) and regulation of gene expression (STATs and Nus proteins). We have also collaborated on a novel antiviral entry inhibitory protein, scytovirin. Using three-dimensional (3D) solution structures and dynamics of proteins and complexes, involving protein-protein, protein-nucleic, and protein-carbohydrate interactions, we elucidate the mechanism of action for these systems and investigate ways to modulate the function. In the STAT system of proteins, we have determined the solution structure of the N-terminal domain of STAT4 and found evidence for a new dimerization interface. Corroborating evidence for this interface is being pursued via investigation of the N-terminal domains (NTDs) of all seven STAT family members. A manuscript describing these studies is being revised for publication. The interactions indicated in the NTD studies have also enabled us to examine the heterodimerization of STAT1 and STAT2 NTDs. These studies are key to understanding the variety of modes of combination among the STAT proteins that can explain the involvement of the seven STAT proteins in literally hundreds of signaling/DNA recognition processes. The studies are being supplemented with further structural determinations for other STAT NTDs.
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