14-3-3 protein
Oxford Dictionary of Biochemistry:
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14-3-3 protein
any of a highly conserved family of proteins, widespread in higher eukaryotes, that seem to act as regulators in signal transduction or phosphorylation. The name derives from the migration position on DEAE-cellulose columns, and on starch-gel electrophoresis, of certain brain proteins that were the first members of the family to be studied. Members of this family have been implicated in regulation of protein kinase C, transcriptional regulation in plants, exocytosis, cell-cycle regulation, and interaction with Raf in the MAP kinase cascade. For example, 14-3-3 protein β (other name: protein kinase C inhibitor protein-1) from sheep activates tyrosine and tryptophan hydroxylases in the presence of Ca2+/calmodulin-dependent protein kinase II. The bovine equivalent has an identical sequence: it is a homodimer.
| 13C-NMR, 11β-hydroxy-4-androstene-3,17-dione, 1-pyrroline-5-carboxylate dehydrogenase | |
| 15-hydroxyprostaglandin dehydrogenase, 17-oxogenic steroid, 17α-hydroxypregnenolone |
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14-3-3 protein
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| Crystal structure of the 14-3-3 zeta:serotonin N-acetyltransferase complex.[1] | |||||||||
| Identifiers | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Symbol | 14-3-3 | ||||||||
| Pfam | PF00244 | ||||||||
| InterPro | IPR000308 | ||||||||
| SMART | 14_3_3 | ||||||||
| PROSITE | PDOC00633 | ||||||||
| SCOP | 1a4o | ||||||||
| SUPERFAMILY | 1a4o | ||||||||
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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.[2]
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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.[3]
14-3-3 regulating cell-signalling
Human Genes
- YWHAA - "14-3-3 alpha"
- YWHAB - "14-3-3 beta"
- YWHAD - "14-3-3 delta"
- YWHAE - "14-3-3 epsilon"
- YWHAG - "14-3-3 gamma"
- YWHAH - "14-3-3 eta"
- YWHAQ - "14-3-3 tau"
- YWHAZ - "14-3-3 zeta"
- YWHAS - "14-3-3 sigma"
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.[4]
Further reading
- Moore BW, Perez VJ (1967). FD Carlson. ed. Physiological and Biochemical Aspects of Nervous Integration. Prentice-Hall, Inc, The Marine Biological Laboratory, Woods Hole, MA. pp. 343–359.
- Mhawech P (2005). "14-3-3 proteins--an update". Cell Res. 15 (4): 228–236. doi:10.1038/sj.cr.7290291. PMID 15857577.
References
- ^ T. Obsil, R. Ghirlando, D. C. Klein, S. Ganguly & F. Dyda (April 2001). "Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation". Cell 105 (2): 257–267. PMID 11336675.
- ^ Takahashi H, Iwata T, Kitagawa Y et al (November 1999). "Increased levels of epsilon and gamma isoforms of 14-3-3 proteins in cerebrospinal fluid in patients with Creutzfeldt-Jakob disease". Clin. Diagn. Lab. Immunol. 6 (6): 983–5. PMC 95810. PMID 10548598. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=95810.
- ^ Cann KL, Hicks GG (2007). "Regulation of the cellular DNA double-strand break response.". Biochem Cell Biol 85 (6): 663–74. doi:10.1139/O07-135. PMID 18059525. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18059525.
- ^ Thomas P. Jahn, Alexander Schulz, Jan Taipalensuu & Michael Gjedde Palmgren (February 2002). "Post-translational modification of plant plasma membrane H(+)-ATPase as a requirement for functional complementation of a yeast transport mutant". The Journal of biological chemistry 277 (8): 6353–6358. doi:10.1074/jbc.M109637200. PMID 11744700.
External links
- Eukaryotic Linear Motif resource motif class LIG_14-3-3_1
- Eukaryotic Linear Motif resource motif class LIG_14-3-3_2
- Eukaryotic Linear Motif resource motif class LIG_14-3-3_3
- MeSH 14-3-3+Protein
- Three-dimensional structure of 14-3-3 Protein Theta (Human) complexed with a peptide in the PDB.
- Drosophila 14-3-3epsilon - The Interactive Fly
- Drosophila 14-3-3zeta - The Interactive Fly
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