Protein-DNA Recognition

Abstract

Understanding how proteins recognize DNA in a sequence-specific manner is central to understanding the regulation of transcription and other cellular processes. I will review the principles of DNA recognition that have emerged from the large number of high-resolution structures determined over the last 10 years. The DNA-binding domains of transcription factors exhibit surprisingly diverse protein architectures, yet all achieve a precise complemetarity of shape facilitating specific chemical recognition of their particular targets. Although general rules for recognition can be derived, the complex nature of the recognition mechanism precludes a simple recognition code. In particular, it has become evident that the structure and flexibility of DNA and contacts mediated by water molecules contribute to the recognition process. Based on the structural information it has proven possible to design proteins with novel recognition specificities. Despite this considerable practical success, the thermodynamic and kinetic properties of protein/DNA recognition remain poorly understood (reviewed in 1).