title: An engineered allosteric switch in leucine-zipper oligomerization.
abstract: Controversy remains about the role of core side-chain packing in specifying protein structure. To investigate the influence of core packing on the oligomeric structure of a coiled coil, we engineered a GCN4 leucine zipper mutant that switches from two to three strands upon binding the hydrophobic ligands cyclohexane and benzene. In solution these ligands increased the apparent thermal stability and the oligomerization order of the mutant leucine zipper. The crystal structure of the peptide-benzene complex shows a single benzene molecule bound at the engineered site in the core of the trimer. These results indicate that coiled coils are well-suited to function as molecular switches and emphasize that core packing is an important determinant of oligomerization specificity.
authors.affiliation: Department of Molecular and cell Biology, University of California, Berkeley,94720-3206, USA.
authors.forename: L
authors.initials: L
authors.lastname: Gonzalez
authors.forename: J J
authors.initials: JJ
authors.lastname: Plecs
authors.forename: T
authors.initials: T
authors.lastname: Alber
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001554:Benzene / Q000378:metabolism; D018360:Crystallography, X-Ray; D003510:Cyclohexanes / Q000378:metabolism; D004268:DNA-Binding Proteins; D004795:Enzyme Stability; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016350:Leucine Zippers / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D015202:Protein Engineering; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D003510:Cyclohexanes; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D001554:Benzene