This large, therapeutically important family of receptors includes the oestrogen, glucocorticoid, thyroid and vitamin D3 receptors amongst many others. In these cases it has been proposed that folding and unfolding events play a critical role in ligand binding. In other cases, the receptors do not bind to molecular chaperones or immunophilins, despite the similarity in structures of the hormone-binding domains of the different receptors. We hope that this work will lead to a better understanding of the exact mode of action of a large, and therapeutically important, class of receptor. The latter is of growing importance since very recent studies on cell cycle proteins have shown that molecular chaperones, such as CDC37 and HSP90, are involved in the association of cyclin-dependent kinases such as CDK4 with cyclins, and also inhibitors of CDKs such as tumour suppressor proteins such as p16.
All projects use similar methodologies.
We use protein engineering techniques to overexpress recombinant protein in bacterial cells, usually, E. coli . We also use stopped-flow methods to study rapid reactions in solution.