Abstract
SUBUNIT oligomerization in many proteins is mediated by short coiled-coil motifs1,2. 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 basis for oligomer choice by characterizing variants3 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, α-helical coiled coil. In contrast to the dimer and tetramer structures3,4, the interior packing of the trimer can accommodate β-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.
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Harbury, P., Kim, P. & Alber, T. Crystal structure of an isoleucine-zipper trimer. Nature 371, 80–83 (1994). https://doi.org/10.1038/371080a0
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DOI: https://doi.org/10.1038/371080a0
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