METAL-ION DEPENDENT MODULATION OF THE DYNAMICS OF A DESIGNED PROTEIN

The peptide a 4 is a designed four-helix bundle that contains a highly simplified hydrophobic core composed exclusively of leucine residues; its tertiary structure is therefore largely dictated by hydrophobic f orces. This small protein adopts a structure with properties intermedi ate between those of the native and molten globule states of proteins: it is compact, globular, and has very stable helices, but its apolar side chains are mobile and not as well packed as in many natural prote ins. To induce a more native-like state, two Zn2+-binding sites were i ntroduced into the protein, thereby replacing some of the nonspecific hydrophobic interactions with more geometrically restrictive metal-lig and interactions. In the metal-bound state, this protein has propertie s that approach those of native proteins. Thus, hydrophobic interactio ns alone are sufficient to drive polypeptide chain folding nearly to c ompletion, but specific interactions are required for a unique structu re.