Raj Kumar, Ph.D., Assistant Professor
Research interests: Steroid receptors (SRs) act in a cell-type and promoter specific manner. SRs have modular structure consisting of three major functional domains, ligand binding- (LBD), DNA binding- (DBD), and N-terminal- (NTD) domains.
Ligand-bound receptor interacts with its specific DNA response element and/or other transcription factors to regulate genes. The basic workings of the DBD and LBD of the SRs are known through a combination of molecular and structural biological approaches. However, little is known about AF1, located in the NTD of SRs. AF1 structure has been difficult to determine because in solutions AF1 seems to exist as a random ensemble of conformers. In terms of sequence homology AF1 domain is the least conserved among the SRs compared to other parts. It is known to interact with other transcription factors, and conditional folding has been reported to be the key for these interactions and subsequent gene regulation. How and what kind of conformation AF1 adopts is an open question. Our laboratory is focused on solving some of these structural/functional issues pertaining to the AF1 of the SRs. We and others have first time discovered methods that might be folding AF1 into a functional conformations. In collaboration with structural biologists at our center as well as out of the campus, we use state-of-art biophysical techniques such as circular dichroism (CD)-, infrared (FTIR)-, NMR and mass- spectroscopies, and X-ray crystallography. Our current interest is focused on the glucocorticoid- and androgen- receptors.
