title: Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily.
abstract: We report the three-dimensional structure of osteogenic protein 1 (OP-1, also known as bone morphogenetic protein 7) to 2.8-A resolution. OP-1 is a member of the transforming growth factor beta (TGF-beta) superfamily of proteins and is able to induce new bone formation in vivo. Members of this superfamily share sequence similarity in their C-terminal regions and are implicated in embryonic development and adult tissue repair. Our crystal structure makes possible the structural comparison between two members of the TGF-beta superfamily. We find that although there is limited sequence identity between OP-1 and TGF-beta 2, they share a common polypeptide fold. These results establish a basis for proposing the OP-1/TGF-beta 2 fold as the primary structural motif for the TGF-beta superfamily as a whole. Detailed comparison of the OP-1 and TGF-beta 2 structures has revealed striking differences that provide insights into how these growth factors interact with their receptors.
authors.affiliation: Rosenstiel Basic Medical Research Center, Brandeis University, Waltham, MA 02254, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Griffith
authors.forename: P C
authors.initials: PC
authors.lastname: Keck
authors.forename: T K
authors.initials: TK
authors.lastname: Sampath
authors.forename: D C
authors.initials: DC
authors.lastname: Rueger
authors.forename: W D
authors.initials: WD
authors.lastname: Carlson
mesh_terms: D001483:Base Sequence; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D003461:Crystallography; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000737:chemistry*
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011506:Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta