title: Crystal structure of the zeta isoform of the 14-3-3 protein.
abstract: The 14-3-3 family of proteins have recently been identified as regulatory elements in intracellular signalling pathways: 14-3-3 proteins bind to oncogene and proto-oncogene products, including c-Raf-1 (refs 2-5), c-Bcr (ref. 6) and polyomavirus middle-T antigen; overexpression of 14-3-3 activates Raf kinase in yeast and induces meiotic maturation in Xenopus oocytes. Here we report the crystal structure of the major isoform of mammalian 14-3-3 proteins at 2.9 A resolution. Each subunit of the dimeric protein consists of a bundle of nine antiparallel helices that form a palisade around an amphipathic groove. The groove is large enough to accommodate a tenth helix, and we propose that binding to an amphipathic helix represents a general mechanism for the interaction of 14-3-3 with diverse cellular proteins. The residues in the dimer interface and the putative ligand-binding surface are invariant among vertebrates, yeast and plants, suggesting a conservation of structure and function throughout the 14-3-3 family.
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Bienkowska
authors.forename: C
authors.initials: C
authors.lastname: Petosa
authors.forename: R J
authors.initials: RJ
authors.lastname: Collier
authors.forename: H
authors.initials: H
authors.lastname: Fu
authors.forename: R
authors.initials: R
authors.lastname: Liddington
mesh_terms: D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003196:Computer Graphics; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D006801:Humans; D007536:Isomerism; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000737:chemistry; D014446:Tyrosine 3-Monooxygenase
chemical_list: D048948:14-3-3 Proteins; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase