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

  title={Crystal structure of the zeta isoform of the 14-3-3 protein},
  author={Dong Liu and Jadwiga R. Bienkowska and Carlo Petosa and R. John Collier and Halan Fu and Robert C. Liddington},
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 Structural Basis for 14-3-3:Phosphopeptide Binding Specificity
Structural basis for protein–protein interactions in the 14-3-3 protein family
Structural detail for five 14-3-3 isoforms bound to ligands is provided, providing structural coverage for all isoforms of a human protein family, and shows that the 14- 3-3 proteins are adaptable structures in which internal flexibility is likely to facilitate recognition and binding of their interaction partners.
A Structural Basis for 14-3-3σ Functional Specificity*♦
It is demonstrated that endogenous 14-3-3σ preferentially forms homodimers in cells and a conserved mechanism for phospho-dependent ligand binding is revealed, implying that the phosphopeptide binding cleft is not the critical determinant of the unique biological properties of 14- 3- 3σ.
The crystal structure of the non-liganded 14-3-3σ protein: insights into determinants of isoform specific ligand binding and dimerization
The crystal structure of the human 14-3-3σ protein was solved at a resolution of 2.8 Å and compared it to the known structures of 14- 3-3ζ and 14-2-3τ and found that the global architecture of the 14-4-4σ fold is similar to the previously determined structures, but the spatial position of the ninth helix differs, indicating adaptability of this part of the molecule.
Role of the 14-3-3 C-terminal region in the interaction with the plasma membrane H+-ATPase.
Results obtained demonstrate that removal of the last 22 amino acids residues of GF14-6 increases binding to H(+)-ATPase and stimulation of its activity, and shows that a peptide reproducing the GF 14-6 C-terminus is able to bind to the C-Terminal domain of H( +)-ATpase and to stimulate the enzyme activity.
Raf-1 Kinase and Exoenzyme S Interact with 14-3-3ζ through a Common Site Involving Lysine 49*
This work identifies the first point mutation (K49E) that dramatically disrupts 14-3-3ζ/ligand interactions and the parallel effects of this single point mutation on both Raf-1 binding and ExoS activation strongly suggest that diverse associated proteins share a common structural binding determinant on 14- 3- 3ζ.
Significance of 14-3-3 self-dimerization for phosphorylation-dependent target binding.
A significant role is established in the role of 14-3-3 dimerization in its ability to bind targets in a phosphorylation-dependent manner and this work points to a mechanism in which 14- 3-3 phosphorylated and Dimerization counterregulate each other.
Characterization of 14-3-3sigma Dimerization Determinants: Requirement of Homodimerization for Inhibition of Cell Proliferation
It is shown that the 14-3-3sigma protein exclusively forms homodimers when it is ectopically expressed at high levels, whereas ectopic 14-2-3zeta formed heterodimerers with the 5 other 14- 3-3 isoforms.


Expression and structural analysis of 14-3-3 proteins.
Protease digestion of intact 14-3-3 showed that the N-terminal half of 14- 3-3 was an intact, dimeric domain of the protein, which may imply that the proteins may adopt a different structural conformation, possibly upon binding to the membrane, which could modulate their activity.
Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation.
A role for 14-3-3 proteins in Raf-mediated signal transduction is suggested, which may participate in or be required for the regulation of Raf function.
Activation of Raf-1 by 14-3-3 proteins
Using the yeast two-hybrid system, two structurally related proteins are identified that interact with the amino-terminal region of Raf-1 and are members of the 14-3-3 family of proteins.
14-3-3 alpha and delta are the phosphorylated forms of raf-activating 14-3-3 beta and zeta. In vivo stoichiometric phosphorylation in brain at a Ser-Pro-Glu-Lys MOTIF.
It is shown by a combination of electrospray mass spectrometry and protein microsequencing that alpha and delta are in vivo post-translationally modified forms of beta and zeta, respectively, and the site of phosphorylation is in a consensus sequence motif for proline-directed kinases.
Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family.
In this study, a protein that interacts with sequences encoded by the first exon of the protein kinase Bcr was cloned and may function in the regulation of c-Bcr and may contribute to the transforming activity of Bcr-Abl in vivo.
The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family.
The cloning and expression of a gene encoding FAS from a bovine brain cDNA library are described and it is demonstrated that purified recombinant FAS produced in Escherichia coli activates ExoS in a defined cell-free system.
Interaction of the protein kinase Raf-1 with 14-3-3 proteins.
Members of a family of highly conserved proteins, termed 14-3-3 proteins, were found by several experimental approaches to associate with Raf-1, a central component of a key signal transduction
Association of polyomavirus middle tumor antigen with 14-3-3 proteins.
Yeast homologs of 14-3-3 proteins have recently been shown to play a role in the timing of mitosis and may contribute to the development of neoplasia.
Stimulatory effects of yeast and mammalian 14-3-3 proteins on the Raf protein kinase.
Bacterially synthesized mammalian 14-3-3 protein stimulated the activity of Raf prepared from yeast cells expressing c-Raf-1, and may participate in or be required for activation of Raf.
Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides
Three-dimensional structures of complexes of the SH2 domain of the v-src oncogene product with two phosphotyrosyl peptides have been determined by X-ray crystallography at resolutions of 1.5 and 2.0