ENGINEERING AN INTERTWINED FORM OF CD2 FOR STABILITY AND ASSEMBLY

The amino-terminal domain of CD2 has the remarkable ability to fold in two ways: either as a monomer or as an intertwined, metastable dimer. Here we show that it is possible to differentially stabilize either f old by engineering the CD2 sequence, mimicking random mutagenesis even ts that could occur during molecular evolution. Crystal structures of a hinge-deletion mutant, which is stable as an intertwined dimer, reve al domain rotations that enable the protein to further assemble to a t etramer. These results demonstrate that a variety of folds can be adop ted by a single polypeptide sequence, and provide guidance for the des ign of proteins capable of further assembly.