دورية أكاديمية
Structural basis for potency differences between GDF8 and GDF11.
| العنوان: | Structural basis for potency differences between GDF8 and GDF11. |
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| المؤلفون: | Walker, Ryan G, Czepnik, Magdalena, Goebel, Erich J, McCoy, Jason C, Vujic, Ana, Cho, Miook, Oh, Juhyun, Aykul, Senem, Walton, Kelly L, Schang, Gauthier, Bernard, Daniel J, Hinck, Andrew P, Harrison, Craig A, Martinez-Hackert, Erik, Wagers, Amy J, Lee, Richard T, Thompson, Thomas B |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1186/s12915-017-0350-1 BMC Biol |
| سنة النشر: | 2017 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Ligands, Myostatin, Receptor, Structure, Transforming growth factor β (TGFβ), Amino Acid Sequence, Animals, Bone Morphogenetic Proteins, Cells, Cultured, Crystallography, X-Ray, Follistatin, Genes, Reporter, Growth Differentiation Factors, Humans, Injections, Intravenous, Luciferases, Mice, Models, Molecular, Myoblasts, Myocardium, Phosphorylation, Protein Binding, Protein Serine-Threonine Kinases, Transforming Growth Factor-beta Type I, Receptors |
| الوصف: | BACKGROUND: Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor β (TGFβ) 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/311626Test |
| DOI: | 10.17863/CAM.58716 |
| الإتاحة: | https://doi.org/10.17863/CAM.58716Test https://www.repository.cam.ac.uk/handle/1810/311626Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.813D4CB9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.58716 |
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