Modulation of DNA-binding domains for sequence-specific DNA recognition

Sequence-specific DNA-binding proteins use diverse mechanisms to recognize their cognate DNA sites. In addition to direct sequence-specific DNA contacts made by DNA recognition domains, extrinsic factors such as ligand binding, homo- and hetero-dimeric protein associations, and association via other transcription factors can also modulate the DNA-recognition properties of DNA-binding domains. In each case, these extrinsic factors act as molecular switches to facilitate cognate DNA recognition. In this article we review the available structural examples of how such extrinsic factors can modulate the way in which a DNA-binding domain can recognize DNA. Together, these examples reveal a variety of ways in which such extrinsic factors can significantly extend the repertoire of DNA sites recognized by a given DNA-binding domain.