14-3-3 Protein - Properties of 14-3-3 Proteins

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 a 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 RXpSXP & Mode 2 RXXp(S/T)X (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.