AN ENGINEERED ALLOSTERIC SWITCH IN LEUCINE-ZIPPER OLIGOMERIZATION

Controversy remains about the role of core side-chain packing in speci fying protein structure. To investigate the influence of core packing on the oligomeric structure of a coiled coil, we engineered a GCN4 leu cine zipper mutant that switches from two to three strands upon bindin g the hydrophobic ligands cyclohexane and benzene. In solution these l igands increased the apparent thermal stability and the oligomerizatio n order of the mutant leucine zipper. The crystal structure of the pep tide-benzene complex shows a single benzene molecule bound at the engi neered site in the core of the trimer. These results indicate that coi led coils are well-suited to function as molecular switches and emphas ize that core packing is an important determinant of oligomerization s pecificity.