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14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. More than 100 signaling proteins have been reported as 14-3-3 ligands. The name 14-3-3 refers to the particular elution and migration pattern of these proteins on DEAE-cellulose chromatography and starch-gel electrophoresis. The 14-3-3 proteins eluted in the 14th fraction of bovine brain homogenate and were found on positions 3.3 of subsequent electrophoresis by Moore and Perez (1967). Elevated amounts of 14-3-3 proteins are found in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.[1] Molecular structure of a 14-3-3 protein dimer bound to a peptide.
Properties of 14-3-3 proteins There are seven genes that encode 14-3-3s in most mammals and 13-15 genes in many higher plants, though typically in fungi they are present only in pairs. Protists have at least one. Eukaryotes can tolerate the loss of an 14-3-3 isoform if multiple isoforms are present, however deletion of all 14-3-3s (as experimentally determined in yeast) results in death. 14-3-3 proteins can be considered evolved members of the Tetratrico Peptide Repeat (TPR) superfamily, generally have 9 or 10 alpha helices, and usually form homo- and/or hetero-dimer interactions along their amino-termini helices. These proteins contain a number of known common modification domains, including regions for divalent cation interaction, phosphorylation & acetylation, and proteolytic cleavage, among others established and predicted. There are common recognition motifs for 14-3-3 proteins that contain a phosphorylated serine or threonine residue; Mode 1 is R[SFYW]XpSXP & Mode 2 RX[SYFWTQAD]Xp(S/T)X[PLM] (where an 'x' can be several, but not all of the 20 amino acids and a lower case 'p' indicates the site of phosphorylation) but also binding to non-phosphorylated ligands has been reported. This interaction occurs along a so called binding groove or cleft that is amphipathic in nature. To date, the crystal structures of six classes of these proteins have been resolved and deposited in the public domain. 14-3-3 proteins play an isoform-specific role in class switch recombination. They are believed to interact with the protein Activation-Induced (Cytidine) Deaminase in mediating class switch recombination. Phosphorylation of Cdc25C by CDS1 and CHK1 creates a binding site for the 14-3-3 family of phosphoserine binding proteins. Binding of 14-3-3 has little effect on Cdc25C activity, and it is believed that 14-3-3 regulates Cdc25C by sequestering it to the cytoplasm, thereby preventing the interactions with CycB-Cdk1 that are localized to the nucleus at the G2/M transition.[2] 14-3-3 regulating cell-signalling Human Genes 14-3-3 in plants Presence of large gene families of 14-3-3 proteins in the Viridiplantae kingdom reflects their essential role in plant physiology. A phylogenetic analysis of 27 plant species clustered the 14-3-3 proteins into four groups. 14-3-3 proteins activate the auto-inhibited plasma membrane P-type H+ ATPases. They bind the ATPases' C-terminus at a conserved threonine.[3] Further reading References External links fa: - - ru: 14-3-3
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