TOWARDS AN UNDERSTANDING OF PROTEIN-DNA RECOGNITION

Understanding how proteins recognize DNA in a sequence-specific manner is central to our understanding of the regulation of transcription an d other cellular processes. In this article we review the principles o f DNA recognition that have emerged from the large number of high-reso lution crystal structures determined over the last 10 years. The DNA-b inding domains of transcription factors exhibit surprisingly diverse p rotein architectures, yet all achieve a precise complementarity of sha pe facilitating specific chemical recognition of their particular DNA targets. Although general rules for recognition can be derived, the co mplex nature of the recognition mechanism precludes a simple recogniti on code. In particular, it has become evident that the structure and f lexibility of DNA and contacts mediated by water molecules contribute to the recognition process. Nevertheless, based on known structures it has proven possible to design proteins with novel recognition specifi cities. Despite this considerable practical success, the thermodynamic and kinetic properties of protein/DNA recognition remain poorly under stood.