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

Nature. 1995 Jul 13;376(6536):191-4. doi: 10.1038/376191a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Computer Graphics
  • Conserved Sequence
  • Crystallography, X-Ray
  • Escherichia coli
  • Humans
  • Isomerism
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Tyrosine 3-Monooxygenase*

Substances

  • 14-3-3 Proteins
  • Proteins
  • Recombinant Proteins
  • Tyrosine 3-Monooxygenase