Thymosin β4 Acetate

Thymosin β4 is also called TB-500. It is a protein that in humans is encoded by the TMSB4X gene. And it is a member of the beta thymosin group, of which there are 15 subtypes reported to date. Beta thymosins are a family of proteins which have in common a sequence of about 40 amino acids similar to the small protein thymosin β4. They are found almost exclusively in multicellular animals. Beta thymosins all possess the amino acid sequence 17-LKKTETQEK-25, which serves as an actin binding site. >> Read More

Thymosin-β4 (Tβ4) sequesters actin monomers to help maintain the high concentrations of unpolymerized actin in higher eukaryotic cells. Despite more than two decades of research investigating the Tβ4–actin interaction, the X-ray structure of the full-length Tβ4:actin complex remained unresolved. Here, we report two X-ray structures of Tβ4:actin complexes. The first structure reveals that Tβ4 has two helices that bind at the barbed and pointed faces of actin, whereas the second structure displays a more open actin nucleotide binding cleft and a disruption of the Tβ4 C-terminal helix interaction. These structures, combined with biochemical assays and molecular dynamics simulations, reveal how Tβ4 prevents monomeric actin from joining actin filaments but participates in the exchange of actin with profilin to ensure controlled actin polymerization.

Xue, B., Leyrat, C., Grimes, J. M., & Robinson, R. C. (2014). Structural basis of thymosin-β4/profilin exchange leading to actin filament polymerization. Proceedings of the National Academy of Sciences, 111(43), E4596-E4605.

The downstream consequences of inflammation in the adult mammalian heart are formation of a non-functional scar, pathological remodelling and heart failure. In zebrafish, hydrogen peroxide released from a wound is the initial instructive chemotactic cue for the infiltration of inflammatory cells, however, the identity of a subsequent resolution signal(s), to attenuate chronic inflammation, remains unknown. Here we reveal that thymosin β4-sulfoxide lies downstream of hydrogen peroxide in the wounded fish and triggers depletion of inflammatory macrophages at the injury site. This function is conserved in the mouse and observed after cardiac injury, where it promotes wound healing and reduced scarring. In human T-cell/CD14+ monocyte co-cultures, thymosin β4-sulfoxide inhibits interferon-γ, and increases monocyte dispersal and cell death, likely by stimulating superoxide production. Thus, thymosin β4-sulfoxide is a putative target for therapeutic modulation of the immune response, resolution of fibrosis and cardiac repair.

Evans, M. A., Smart, N., Dubé, K. N., Bollini, S., Clark, J. E., Evans, H. G., ... & Mills, K. (2013). Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing. Nature communications, 4, 2081.