How structural biology transformed studies of transcription regulation

The past 4 decades have seen remarkable advances in our understanding of the structural basis of gene regulation. Technological advances in protein expression, nucleic acid synthesis, and structural biology made it possible to study the proteins that regulate transcription in the context of ever larger complexes containing proteins bound to DNA. This review, written on the occasion of the 50th anniversary of the founding of the Protein Data Bank focuses on the insights gained from structural studies of protein–DNA complexes and the role the PDB has played in driving this research. I cover highlights in the field, beginning with X-ray crystal structures of the first DNA-binding domains to be studied, through recent cryo-EM structures of transcription factor binding to nucleosomal DNA.