NMR structural studies on the zinc finger domains of nuclear hormone receptors

This chapter presents an overview of the application of modern NMR methods in structural studies of the DNA binding domains (DBDs) of nuclear hormone receptors. The DBDs studied so far comprise those of the glucocorticoid, estrogen, retinoic acid and retinoid X receptors. NMR spectroscopy has allowed the elucidation of the first structures of this family of C4-type zinc fingers, which led to a better understanding of their role in gene regulation. Crystallographic studies provided insight in protein-protein and protein-DNA interactions. Subsequent studies, applying NMR, have provided deeper insight into a diversity of issues concerning these proteins, ranging from backbone dynamics and metal coordination to the interaction of these domains with their DNA target sites. From this work a picture emerges of a class of closely related zinc-binding proteins which, despite their strong sequence homology, exhibit interesting structural and functional differences between members of different subfamilies.