Interactions between transcription factors bound to separate operator sites commonly play an important role in gene regulation by mediating cooperative binding to the DNA. However, few detailed structural models for understanding the molecular basis of such cooperativity are available. The cl repressor of bacteriophage λ is a classic example of a protein that binds to its operator sites cooperatively. The C-terminal domain of the repressor mediates dimerization as well as a dimer-dimer interaction that results in the cooperative binding of two repressor dimers to adjacent operator sites. Here, we present the x-ray crystal structure of the λ repressor C-terminal domain determined by multiwavelength anomalous diffraction. Remarkably, the interactions that mediate cooperativity are captured in the crystal, where two dimers associate about a 2-fold axis of symmetry. Based on the structure and previous genetic and biochemical data, we present a model for the cooperative binding of two λ repressor dimers at adjacent operator sites.
Bell, C. E., Frescura, P., Hochschild, A., & Lewis, M. (2000). Crystal structure of the λ repressor C-terminal domain provides a model for cooperative operator binding. Cell, 101(7), 801–811. https://doi.org/10.1016/S0092-8674(00)80891-0