No abstract

The crystal structure of the arabinose-binding and dimerization domain of the Escherchia coli gene regulatory protein AraC was determined in the presence and absence of L-arabinose. The 1.5 angstrom structure of the arabinose-bound molecule shows that the protein adopts an unusual fold, binding sugar within a beta barrel and completely burying the arabinose with the amino-terminal arm of the protein. Dimer contacts in the presence of arabinose are mediated by an antiparallel coiled-coil. In the 2.8 angstrom structure of the uncomplexed protein, the amino-terminal arm is disordered, uncovering the sugar-binding pocket and allowing it to serve as an oligomerization interface. The ligand-gated oligomerization as seen in AraC provides the basis of a plausible mechanism for modulating the protein's DNA-looping properties.

DNA looping is widely used in nature. It is well documented in the regulation of prokaryotic and eukaryotic gene expression, DNA replication, and site-specific DNA recombination. Undoubtedly looping also functions in other protein-DNA transactions such as repair and chromosome segregation. While the underlying physical chemistry of DNA looping is common to all systems, the precise biochemical details of looping and the utilization of looping by different systems varies widely. Looping appears to have been chosen by nature in such a wide variety of contexts because it solves problems both of binding and of geometry. The cooperativity inherent in binding a protein to multiple sites on DNA facilitates high occupancy of DNA sites by low concentrations of proteins. DNA looping permits a sizeable number of DNA-binding proteins to interact with one of their number, for example RNA polymerase. Finally, DNA looping may simplify evolution by not requiring a precise spacing between a protein's binding site and a second site on the DNA.