The PAS domain is a ligand binding and protein-protein interaction domain found in archaea, prokaryotes and eukaryotes. We are interested in how PAS domains select between dimerization partners in mammalian bHLH-PAS transcription factors. This work is an extension of our work with the bHLH factor NeuroD1, which selectively heterodimerizes with E47. We are currently studying how multiple bHLH-PAS factors including Sim, SS, SIMA and TRH selectively heterodimerize with Tango, but cannot homodimerize.

We are expressing the bHLH and PAS domains of these factors and testing their ability to form homo- and heterodimers. We are using gel shift assays to address how the PAS domain alters the DNA binding properties of the bHLH domain. Finally, we are screening conditions for crystallization of bHLH-PAS constructs.

This project is in collaboration with Pat Estes, in the Department of Genetics at NCSU, who studies the role of PAS proteins in drosophila nervous system development.