Xing Lab Reveals Structure of Cell Sensor for Cancer Signals and Toxins

A new study from Dr. Yongna Xing’s group at the University of Wisconsin Carbone Cancer Center (UWCCC) and the McArdle Laboratory for Cancer Research, recently published in the journal Proceedings of the National Academy of Sciences, solved the structure of the aryl hydrocarbon receptor (AHR) transcriptional complex. AHR responds to diverse chemicals and cellular metabolites that might cause different biological consequences, from toxicity responses, development, to normal functions of immune and cardiovascular systems.  AHR is inactive in cells until it interacts with one of its chemical signals, known as ligands. Then, AHR changes its shape, exposing a part of the receptor that directs it to enter the nucleus – nuclear localization signal (NLS). Once in the nucleus, where all the cell’s DNA resides, AHR partners with another protein, ARNT, and together they increase the expression of genes which correspond to the chemical signal which the AHR receptor protein “received.” In the structure, Xing and colleagues, including oncology professor Dr. Christopher Bradfield, show how AHR and ARNT interact with each other and with target DNA. Because of its higher structural flexibility, AHR is able to adopt more changes in the protein structure upon chemical activation than other transcription factors in the same family. This would allow AHR to adopt different conformations upon binding to different ligands. The structure underlies highly integrative, naturally-evolved protein machinery for versatile responses to many different environmental and chemical cues to create different biological outputs.