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Crystal structure of the zeta isoform of the 14-3-3 protein

Nature volume 376, pages 191–194 (1995)Cite this article

Abstract

THE 14-3-3 family of proteins have recently been identified as regulatory elements in intracellular signalling pathways1: 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 antigen7; overexpression of 14-3-3 activates Raf kinase in yeast2,3 and induces meiotic maturation in Xenopus oocytes5. Here we report the crystal structure of the major isoform of mammalian 14-3-3 proteins at 2.9 Å 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.

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Author notes

  1. R. John Collier: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA

  2. Halan Fu: Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA

Authors and Affiliations

  1. Dana–Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 44 Binney Street, Boston, Massachusetts, 02115, USA

    Dong Liu, Jadwiga Bienkowska, Carlo Petosa, R. John Collier, Halan Fu & Robert Liddington

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  1. Dong Liu
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  2. Jadwiga Bienkowska
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  3. Carlo Petosa
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  4. R. John Collier
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  5. Halan Fu
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  6. Robert Liddington
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Liu, D., Bienkowska, J., Petosa, C. et al. Crystal structure of the zeta isoform of the 14-3-3 protein. Nature 376, 191–194 (1995). https://doi.org/10.1038/376191a0

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