A SWITCH BETWEEN 2-STRANDED, 3-STRANDED AND 4-STRANDED COILED COILS IN GCN4 LEUCINE-ZIPPER MUTANTS

Coiled-coil sequences in proteins consist of heptad repeats containing two characteristic hydrophobic positions. The role of these buried hy drophobic residues in determining the structures of coiled coils was i nvestigated by studying mutants of the GCN4 leucine zipper. When sets of buried residues were altered, two-, three-, and four-helix structur es were formed. The x-ray crystal structure of the tetramer revealed a parallel, four-stranded coiled coil. In the tetramer conformation, th e local packing geometry of the two hydrophobic positions in the hepta d repeat is reversed relative to that in the dimer. These studies demo nstrate that conserved, buried residues in the GCN4 leucine zipper dir ect dimer formation. In contrast to proposals that the pattern of hydr ophobic and polar amino acids in a protein sequence is sufficient to d etermine three-dimensional structure, the shapes of buried side chains in coiled coils are essential determinants of the global fold.