Structural basis for potency differences between GDF8 and GDF11.
BMC Biol
; 15(1): 19, 2017 03 03.
Article
in En
| MEDLINE
| ID: mdl-28257634
ABSTRACT
BACKGROUND:
Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor ß (TGFß) 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 GDF11FS288 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone Morphogenetic Proteins
/
Growth Differentiation Factors
/
Myostatin
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
BMC Biol
Journal subject:
BIOLOGIA
Year:
2017
Type:
Article
Affiliation country:
United States