G3DSA:1.20.190.20

14-3-3 domain

CATH-Gene3D entry
Member databaseCATH-Gene3D
CATH-Gene3D typehomologous superfamily

Description
Imported from IPR036815

The 14-3-3 proteins are a large family of approximately 30kDa acidic proteins which exist primarily as homo- and heterodimers within all eukaryotic cells
[2, 1]
. These are structurally similar phospho-binding proteins that regulate multiple signaling pathways
[3]
. There is a high degree of sequence identity and conservation between all the 14-3-3 isotypes, particularly in the regions which form the dimer interface or line the central ligand binding channel of the dimeric molecule. Each 14-3-3 protein sequence can be roughly divided into three sections: a divergent amino terminus, the conserved core region and a divergent carboxyl terminus. The conserved middle core region of the 14-3-3s encodes an amphipathic groove that forms the main functional domain, a cradle for interacting with client proteins. The monomer consists of nine helices organised in an antiparallel manner, forming an L-shaped structure. The interior of the L-structure is composed of four helices: H3 and H5, which contain many charged and polar amino acids, and H7 and H9, which contain hydrophobic amino acids. These four helices form the concave amphipathic groove that interacts with target peptides.

The 14-3-3 proteins mainly bind proteins containing phosphothreonine or phosphoserine motifs, however exceptions to this rule do exist. Extensive investigation of the 14-3-3 binding site of the mammalian serine/threonine kinase Raf-1 has produced a consensus sequence for 14-3-3-binding, RSxpSxP (in the single-letter amino-acid code, where x denotes any amino acid and p indicates that the next residue is phosphorylated). The 14-3-3 proteins appear to effect intracellular signalling in one of three ways - by direct regulation of the catalytic activity of the bound protein, by regulating interactions between the bound protein and other molecules in the cell by sequestration or modification or by controlling the subcellular localisation of the bound ligand. Proteins appear to initially bind to a single dominant site and then subsequently to many, much weaker secondary interaction sites. The 14-3-3 dimer is capable of changing the conformation of its bound ligand whilst itself undergoing minimal structural alteration.

References
Imported from IPR036815

1.How do 14-3-3 proteins work?-- Gatekeeper phosphorylation and the molecular anvil hypothesis. Yaffe MB. FEBS Lett. 513, 53-7, (2002). View articlePMID: 11911880

2.Distinct forms of the protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. Isobe T, Ichimura T, Sunaya T, Okuyama T, Takahashi N, Kuwano R, Takahashi Y. J. Mol. Biol. 217, 125-32, (1991). View articlePMID: 1671102

3.The dynamic and stress-adaptive signaling hub of 14-3-3: emerging mechanisms of regulation and context-dependent protein-protein interactions. Pennington KL, Chan TY, Torres MP, Andersen JL. Oncogene 37, 5587-5604, (2018). PMID: 29915393

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.