CRYSTAL-STRUCTURE OF AN ISOLEUCINE-ZIPPER TRIMER

SUBUNIT oligomerization in many proteins is mediated by short coiled-c oil motifs(1,2). These motifs share a characteristic seven-amino-acid repeat containing hydrophobic residues at the first (a) and fourth (d) positions. Despite this common pattern, different sequences form two- , three- and four-stranded helical ropes. We have investigated the bas is for oligomer choice by characterizing variants(3) of the GCN4 lenci ne-zipper dimerization domain that adopt trimeric or tetrameric struct ures in response to mutations at the a and d positions. We now report the high-resolution X-ray crystal structure of an isoleucine-containin g mutant that folds into a parallel three-stranded, alpha-helical coil ed coil. In contrast to the dimer and tetramer structures(3,4), the in terior packing of the trimer can accommodate beta-branched residues in the most preferred rotamer at both hydrophobic positions. Compatibili ty of the shape of the core amino acids with the distinct packing spac es in the two-, three- and four-stranded conformations appears to dete rmine the oligomerization state of the GCN4 leucine-zipper variants.