Role of the 14‐3‐3 C‐terminal loop in ligand interaction

@article{Truong2002RoleOT,
  title={Role of the 14‐3‐3 C‐terminal loop in ligand interaction},
  author={A Truong and Shane C. Masters and Hongzhu Yang and Haian Fu},
  journal={Proteins: Structure},
  year={2002},
  volume={49}
}
14‐3‐3 proteins are a family of conserved dimeric molecules that interact with a broad range of target proteins, most of which contain phosphoserine/threonine. The amphipathic groove of 14‐3‐3 is the main structural feature involved in mediating its associations. We have studied another domain of 14‐3‐3, the C‐terminal loop, to determine what role it plays in ligand interaction. A truncated form of 14‐3‐3ζ lacking this C‐terminal loop was generated and found to bind with higher affinity than… 
14‐3‐3 protein binding blocks the dimerization interface of caspase‐2
TLDR
The data reveal that the 14‐3‐3 dimer interacts with proC2 not only through ligand‐binding grooves but also through other regions outside the central channel, thus explaining the isoform‐dependent specificity of 14‐ 3‐3 protein binding to proC1 and the substantially higher binding affinity of 14-3‐ 3 protein to pro caspase than to the doubly phosphorylated peptide.
Isoform‐specific cleavage of 14‐3‐3 proteins in apoptotic JURL‐MK1 cells
TLDR
It is suggested that the processing of 14‐3‐3 proteins could form an integral part of the programmed cell death or at least of some apoptotic pathways.
BCR kinase phosphorylates 14‐3‐3 Tau on residue 233
TLDR
It is shown here that BCR interacts with at least five isoforms of 14‐3‐3 in vivo and phosphorylates 14‐ 3‐3τ on Ser233 and to a lesser extent 14‐2‐3ζ on Thr233.
Exposed Loop Domains of Complexed 14-3-3 Proteins Contribute to Structural Diversity and Functional Specificity1
TLDR
The epitopes for three unique monoclonal antibodies developed against the Arabidopsis G-box DNA:protein complex were determined, demonstrating the functional significance of the surface accessible, evolutionarily distinct loop 8 domain.
NMR spectroscopy of 14-3-3ζ reveals a flexible C-terminal extension: differentiation of the chaperone and phosphoserine-binding activities of 14-3-3ζ.
TLDR
1H-NMR spectroscopy revealed the presence of a flexible and unstructured C-terminal extension, 12 amino acids in length, which protrudes from the domain core of 14-3-3ζ and is similar in structure and length to the C-Terminal extension of mammalian sHsps.
Role of the 14-3-3 C-terminal region in the interaction with the plasma membrane H+-ATPase.
TLDR
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.
Structural basis of 14-3-3 protein functions.
14-3-3 Protein C-terminal Stretch Occupies Ligand Binding Groove and Is Displaced by Phosphopeptide Binding*
TLDR
Intramolecular distances calculated from FRET measurements fit well with distances obtained from molecular dynamics simulation of full-length 14-3-3ζ protein, and phosphopeptide binding displaces the C-terminal stretch from the ligand binding groove.
The Functional Interaction of 14-3-3 Proteins with the ERK1/2 Scaffold KSR1 Occurs in an Isoform-specific Manner*
TLDR
It is demonstrated, both in vitro and in vivo, a specific, functionally relevant interaction of human 14-3-3γ with the molecular scaffold KSR1, which is mediated by the C-terminal stretch of 14-2-3α, the cytosolic anchor that keeps K SR1 inactive.
...
...

References

SHOWING 1-10 OF 21 REFERENCES
Crystal structure of the zeta isoform of the 14-3-3 protein
TLDR
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.
Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways
TLDR
The crystal structure of the human T-cell 14-3-3 isoform (τ) dimer at 2.6 Å resolution is reported, which creates a large, negatively charged channel which has been implicated in the binding of 14- 3-3 to protein kinase C.
Raf-1 Kinase and Exoenzyme S Interact with 14-3-3ζ through a Common Site Involving Lysine 49*
TLDR
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.
The Structural Basis for 14-3-3:Phosphopeptide Binding Specificity
14-3-3 proteins: structure, function, and regulation.
TLDR
This review examines the structural basis for 14-3- 3-ligand interactions, proposed functions of 14-1-3 in various signaling pathways, and emerging views of mechanisms that regulate 14-2-3 actions.
14-3-3 inhibits Bad-induced cell death through interaction with serine-136.
TLDR
A critical role for 14-3-3 in regulating Bad proapoptotic activity is demonstrated, which is controlled largely by phosphorylation of S136, whereas S112 may represent a 14- 3-3 -independent pathway.
Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display.
TLDR
A well-defined peptide will be an effective tool for probing the role of 14-3-3 in various signaling pathways, and may lead to the development of high-affinity antagonists with pharmacological applications.
14-3-3ζ Binds a Phosphorylated Raf Peptide and an Unphosphorylated Peptide via Its Conserved Amphipathic Groove*
TLDR
The ability of each groove to bind different peptide motifs suggests how 14-3-3 can act in signal transduction by inducing either homodimer or heterodimer formation in its target proteins.
...
...