- 14-3-3 protein
14-3-3 proteins are a family of conserved regulatory
molecule s expressed in all eukaryotic cells. 14-3-3protein s have the ability to bind a multitude of functionally diverse signaling proteins, includingkinase s,phosphatase s, andtransmembrane receptor s. More than 100 signaling proteins have been reported as 14-3-3 ligands.The name 14-3-3 refers to the characteristic migration pattern of these proteins on electrophoretic gels.
Elevated amounts of 14-3-3 proteins are found in the
cerebrospinal fluid of patients withCreutzfeldt-Jakob disease .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, some algae, and other 'lower' forms of life 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 isamphipathic 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 regulating cell-signalling
*Raf-1
*Bad - seeBcl-2
*Bax
*Cdc25 Genes
* - "
14-3-3 alpha "
* - "14-3-3 beta "
* - "14-3-3 delta "
* - "14-3-3 epsilon"
* - "14-3-3 gamma "
* - "14-3-3 eta "
* - "14-3-3 tau "
* - "14-3-3 zeta"References
*
External links
*
* [http://www.rcsb.org/pdb/explore.do?structureId=2BTP Three-dimensional structure of 14-3-3 Protein Theta (Human) complexed with a peptide in the PDB.]
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