title: Crystal structure of human GDF11.
abstract: Members of the TGF-β family of proteins are believed to play critical roles in cellular signaling processes such as those involved in muscle differentiation. The extent to which individual family members have been characterized and linked to biological function varies greatly. The role of myostatin, also known as growth differentiation factor 8 (GDF8), as an inhibitor of muscle differentiation is well understood through genetic linkages. In contrast, the role of growth differentiation factor 11 (GDF11) is much less well understood. In humans, the mature forms of GDF11 and myostatin are over 94% identical. In order to understand the role that the small differences in sequence may play in the differential signaling of these molecules, the crystal structure of GDF11 was determined to a resolution of 1.50 Å. A comparison of the GDF11 structure with those of other family members reveals that the canonical TGF-β domain fold is conserved. A detailed structural comparison of GDF11 and myostatin shows that several of the differences between these proteins are likely to be localized at interfaces that are critical for the interaction with downstream receptors and inhibitors.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Padyana
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Bhamini
authors.initials: B
authors.lastname: Vaidialingam
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Hayes
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Franti
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Farrow
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D055412:Growth Differentiation Factors / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D055435:Myostatin / Q000737:chemistry; D000072756:Protein Conformation, alpha-Helical; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; D055412:Growth Differentiation Factors; D055435:Myostatin
keywords: GDF11; TGF-β family; growth differentiation factor 11