Crystal structure of an isoleucine-zipper trimer.
Subunit oligomerization in many proteins is mediated by short coiled-coil motifs. 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 basis for oligomer choice by characterizing variants of the GCN4 leucine-zipper dimerization domain that adopt trimeric or tetrameric structures in response to mutations at the a and d positions. We now report the high-resolution X-ray crystal structure of an isoleucine-containing mutant that folds into a parallel three-stranded, alpha-helical coiled coil. In contrast to the dimer and tetramer structures, the interior packing of the trimer can accommodate beta-branched residues in the most preferred rotamer at both hydrophobic positions. Compatibility of the shape of the core amino acids with the distinct packing spaces in the two-, three- and four-stranded conformations appears to determine the oligomerization state of the GCN4 leucine-zipper variants.
Harbury
P B
PB
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Kim
P S
PS
Alber
T
T
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry*; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases