| First Author | Walker RG | Year | 2017 |
| Journal | BMC Biol | Volume | 15 |
| Issue | 1 | Pages | 19 |
| PubMed ID | 28257634 | Mgi Jnum | J:242410 |
| Mgi Id | MGI:5905208 | Doi | 10.1186/s12915-017-0350-1 |
| Citation | Walker RG, et al. (2017) Structural basis for potency differences between GDF8 and GDF11. BMC Biol 15(1):19 |
| abstractText | BACKGROUND: Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor beta (TGFbeta) family. While GDF8 has been recognized as a negative regulator of muscle growth and differentiation, there are conflicting studies on the function of GDF11 and whether GDF11 has beneficial effects on age-related dysfunction. To address whether GDF8 and GDF11 are functionally identical, we compared their signaling and structural properties. RESULTS: Here we show that, despite their high similarity, GDF11 is a more potent activator of SMAD2/3 and signals more effectively through the type I activin-like receptor kinase receptors ALK4/5/7 than GDF8. Resolution of the GDF11:FS288 complex, apo-GDF8, and apo-GDF11 crystal structures reveals unique properties of both ligands, specifically in the type I receptor binding site. Lastly, substitution of GDF11 residues into GDF8 confers enhanced activity to GDF8. CONCLUSIONS: These studies identify distinctive structural features of GDF11 that enhance its potency, relative to GDF8; however, the biological consequences of these differences remain to be determined. |
