Beta thymosins

Source: Wikipedia, the free encyclopedia.
orthologue
of human β10

Beta thymosins are a family of proteins which have in common a sequence of about 40 amino acids similar to the small protein

thymosins
" are now known to be structurally and genetically unrelated and present in many different animal tissues.

Single domain β-thymosins

Distribution

Thymosin beta-4 family
SCOP2
1hj0 / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1hj0​, 1sqk​, 1t44​, 2ff6​

Bony fish in general express orthologues of these same three, plus an additional copy of the β4 orthologue.[9]

family gene locus protein
β4 TMSB4X Chr. X q21.3-q22 Thymosin β4
TMSB4Y Chr. Y Thymosin β4,
Y-chromosomal
β10 TMSB10
Chr. 2 p11.2
 Thymosin β10
β15 TMSB15A Chr. X q21.33-q22.3 Thymosin β15
TMSB15B Chr. X q22.2 Thymosin β15

Thymosin β1 was found to be ubiquitin (truncated by two C-terminal glycine residues).[10]

Relation to the WH2 sequence module

The N-terminal half of β-thymosins bears a strong similarity in

Wiskott-Aldrich syndrome protein).[11][12] Evidence from X-ray crystallography shows that this part of β-thymosins binds to actin in a near-identical manner to that of WH2 modules, both adopting as they bind, a conformation which has been referred to as the β-thymosin/WH2 fold. β-thymosins may therefore have evolved by addition of novel C-terminal sequence to an ancestral WH2 module.[13] However, sequence similarity searches designed to identify present-day WH2 domains[14] fail to recognise β-thymosins, (and vice versa) and the sequence and functional similarities may result from convergent evolution.[15]

Biological activities of thymosin β4

Further information: Thymosin beta-4

The archetypical β-thymosin is β4 (product in humans of the TMSB4X gene), which is a major cellular constituent in many tissues. Its intracellular concentration may reach as high as 0.5 mM.[10] Following Thymosin α1, β4 was the second of the biologically active peptides from Thymosin Fraction 5 to be completely sequenced and synthesized.[16]

Due to its profusion in the cytosol and its ability to bind G-actin but not F-actin, thymosin β4 is regarded as the principal actin-sequestering protein in many cell types.[17]

Clinical applications

Thymosin β4 has been tested in multicenter trials sponsored jointly by RegeneRx Biopharmaceuticals Inc (Rockville, MD, USA) and Sigma Tau (Pomezia, Italy) in the United States and Europe in patients with

venostasis, and Epidermolysis bullosa simplex
and was found to accelerate bed sore and stasis ulcer repair by one month. It has also been tested in patients with chronic neurotrophic corneal epithelial defects and found to promote repair.

Thymosin β15 : Levels of human thymosin β15 in urine have shown promise as a diagnostic marker for prostate cancer which is sensitive to potential aggressiveness of the tumour [18]

Doping in sports

Thymosin beta-4 was allegedly used by some players in various Australian football codes.[19]

β-thymosin repeat proteins

NMR structure of bovine β9-thymosin, the orthologue of human β10.[20] Rainbow coloured where the N-terminus = blue and the C-terminus
= red.

Distribution

These proteins, which typically contain 2-4 repeats of the β-thymosin sequence, are found in all phyla of the animal kingdom, with the probable exception of sponges[21] The sole mammalian example, a dimer in mice, is synthesised by transcriptional read-through between two copies of the mouse β15 gene, each of which is also transcribed separately.[22] A uniquely multiple example is the protein thypedin of Hydra which has 27 repeats of a β-thymosin sequence.[23]

Biological activities

β-thymosin repeat proteins resemble the monomeric forms in being able to bind to actin, but sequence differences in one example studied, a three-repeat protein Ciboulot of the fruit fly Drosophila, allow binding to ends of actin filaments, an activity which differs from monomer sequestration.[24]

These proteins became of interest in neurobiology with the finding that in the nudibranch (sea slug)

sensory neurons in the conditioned stimulus pathway,[25] and in multi-trial Pavlovian conditioning.[26] The phosphorylation of Csp24, in common with post-translational modifications of a number of cytoskeleton-related proteins may contribute to actin-filament dynamics underlying structural remodeling of responsive cells.[26]

See also

References

  1. S2CID 39655090
    .
  2. PMID 9108730
    . The thymosin is β9, bovine orthologue of human β10. Stabilised by organic solvent, the structure was determined by NMR. (Free β-thymosins lack a stable fold in solution)
  3. PMID 9108730
    .
  4. ^ "Family: Thymosin (PF01290)". Pfam. Wellcome Trust Sanger Institute. Archived from the original on 2008-01-26.
  5. PMID 18461162
    .
  6. ^ "XYM2758.rev XYM Monosiga brevicollis rapidly growi... - EST result". 2008-03-20. {{cite journal}}: Cite journal requires |journal= (help)
  7. ^ "NUE00005552 Capsaspora owczarzaki Amplicon express Capsaspora owczarza - EST - NCBI". 2008-11-20. {{cite journal}}: Cite journal requires |journal= (help).
  8. S2CID 8675540
    .
  9. PMID 20138884
    .
  10. ^
    S2CID 222082792
    .
  11. PMID 11911886
    .
  12. ^ "Family: WH2 (PF02205)". Pfam. Wellcome Trust Sanger Institute.[permanent dead link]
  13. S2CID 222086831
    .
  14. ^ "Family: WH2 (PF02205)". Pfam. Wellcome Trust Sanger Institute.[permanent dead link]
  15. PMID 15328003
    .
  16. PMID 6940133
    .
  17. ISBN 978-0-7167-3706-3
    .
  18. S2CID 71453198
    .
  19. ^ "Cronulla Sharks and thymosin beta-4 … is it doping?".
  20. PMID 9108730
    . The thymosin is β9, bovine orthologue of human β10. Stabilised by organic solvent, the structure was determined by NMR. (Free β-thymosins lack a stable fold in solution)
  21. ISBN 978-0-387-46407-7
    .
  22. PMID 19233202
    .
  23. PMID 16169708
    .
  24. S2CID 22521722
    .
  25. S2CID 35463597
    .
  26. ^
    PMID 19961907
    .
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