• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jan 23, 1996; 93(2): 878–883.

Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily.


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sampath TK, Coughlin JE, Whetstone RM, Banach D, Corbett C, Ridge RJ, Ozkaynak E, Oppermann H, Rueger DC. Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily. J Biol Chem. 1990 Aug 5;265(22):13198–13205. [PubMed]
  • Cook SD, Wolfe MW, Salkeld SL, Rueger DC. Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates. J Bone Joint Surg Am. 1995 May;77(5):734–750. [PubMed]
  • Ozkaynak E, Schnegelsberg PN, Oppermann H. Murine osteogenic protein (OP-1): high levels of mRNA in kidney. Biochem Biophys Res Commun. 1991 Aug 30;179(1):116–123. [PubMed]
  • Helder MN, Ozkaynak E, Sampath KT, Luyten FP, Latin V, Oppermann H, Vukicevic S. Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in human and mouse development. J Histochem Cytochem. 1995 Oct;43(10):1035–1044. [PubMed]
  • Perides G, Jensen FE, Edgecomb P, Rueger DC, Charness ME. Neuroprotective effect of human osteogenic protein-1 in a rat model of cerebral hypoxia/ischemia. Neurosci Lett. 1995 Feb 24;187(1):21–24. [PubMed]
  • Lefer AM, Tsao PS, Ma XL, Sampath TK. Anti-ischaemic and endothelial protective actions of recombinant human osteogenic protein (hOP-1). J Mol Cell Cardiol. 1992 Jun;24(6):585–593. [PubMed]
  • Kingsley DM. The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 1994 Jan;8(2):133–146. [PubMed]
  • Daopin S, Piez KA, Ogawa Y, Davies DR. Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily. Science. 1992 Jul 17;257(5068):369–373. [PubMed]
  • Schlunegger MP, Grütter MG. An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2. Nature. 1992 Jul 30;358(6385):430–434. [PubMed]
  • Ozkaynak E, Rueger DC, Drier EA, Corbett C, Ridge RJ, Sampath TK, Oppermann H. OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. EMBO J. 1990 Jul;9(7):2085–2093. [PMC free article] [PubMed]
  • Sampath TK, Maliakal JC, Hauschka PV, Jones WK, Sasak H, Tucker RF, White KH, Coughlin JE, Tucker MM, Pang RH, et al. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem. 1992 Oct 5;267(28):20352–20362. [PubMed]
  • Griffith DL, Oppermann H, Rueger DC, Sampath TK, Tucker RF, Carlson WD. Crystallization and preliminary crystallographic data of recombinant human osteogenic protein-1 (hOP-1). J Mol Biol. 1994 Dec 16;244(5):657–658. [PubMed]
  • TenEyck LF, Arnone A. Three-dimensional Fourier synthesis of human deoxyhemoglobin at 2-5 A resolution I. X-ray analysis. J Mol Biol. 1976 Jan 5;100(1):3–11. [PubMed]
  • Wang BC. Resolution of phase ambiguity in macromolecular crystallography. Methods Enzymol. 1985;115:90–112. [PubMed]
  • Jones TA, Zou JY, Cowan SW, Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991 Mar 1;47(Pt 2):110–119. [PubMed]
  • Brünger AT, Kuriyan J, Karplus M. Crystallographic R factor refinement by molecular dynamics. Science. 1987 Jan 23;235(4787):458–460. [PubMed]
  • Lee B, Richards FM. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379–400. [PubMed]
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer EF, Jr, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. [PubMed]
  • Gilson MK, Honig BH. Calculation of electrostatic potentials in an enzyme active site. Nature. 1987 Nov 5;330(6143):84–86. [PubMed]
  • McDonald NQ, Hendrickson WA. A structural superfamily of growth factors containing a cystine knot motif. Cell. 1993 May 7;73(3):421–424. [PubMed]
  • Oefner C, D'Arcy A, Winkler FK, Eggimann B, Hosang M. Crystal structure of human platelet-derived growth factor BB. EMBO J. 1992 Nov;11(11):3921–3926. [PMC free article] [PubMed]
  • Lapthorn AJ, Harris DC, Littlejohn A, Lustbader JW, Canfield RE, Machin KJ, Morgan FJ, Isaacs NW. Crystal structure of human chorionic gonadotropin. Nature. 1994 Jun 9;369(6480):455–461. [PubMed]
  • Wu H, Lustbader JW, Liu Y, Canfield RE, Hendrickson WA. Structure of human chorionic gonadotropin at 2.6 A resolution from MAD analysis of the selenomethionyl protein. Structure. 1994 Jun 15;2(6):545–558. [PubMed]
  • Leszczynski JF, Rose GD. Loops in globular proteins: a novel category of secondary structure. Science. 1986 Nov 14;234(4778):849–855. [PubMed]
  • Sibanda BL, Thornton JM. Conformation of beta hairpins in protein structures: classification and diversity in homologous structures. Methods Enzymol. 1991;202:59–82. [PubMed]
  • McDonald NQ, Lapatto R, Murray-Rust J, Gunning J, Wlodawer A, Blundell TL. New protein fold revealed by a 2.3-A resolution crystal structure of nerve growth factor. Nature. 1991 Dec 5;354(6352):411–414. [PubMed]
  • Stenzel P, Angerer LM, Smith BJ, Angerer RC, Vale WW. The univin gene encodes a member of the transforming growth factor-beta superfamily with restricted expression in the sea urchin embryo. Dev Biol. 1994 Nov;166(1):149–158. [PubMed]
  • Arora K, Levine MS, O'Connor MB. The screw gene encodes a ubiquitously expressed member of the TGF-beta family required for specification of dorsal cell fates in the Drosophila embryo. Genes Dev. 1994 Nov 1;8(21):2588–2601. [PubMed]
  • Storm EE, Huynh TV, Copeland NG, Jenkins NA, Kingsley DM, Lee SJ. Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Nature. 1994 Apr 14;368(6472):639–643. [PubMed]
  • Chang SC, Hoang B, Thomas JT, Vukicevic S, Luyten FP, Ryba NJ, Kozak CA, Reddi AH, Moos M., Jr Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development. J Biol Chem. 1994 Nov 11;269(45):28227–28234. [PubMed]
  • H tten G, Neidhardt H, Schneider C, Pohl J. Cloning of a new member of the TGF-beta family: a putative new activin beta C chain. Biochem Biophys Res Commun. 1995 Jan 17;206(2):608–613. [PubMed]
  • Cunningham NS, Jenkins NA, Gilbert DJ, Copeland NG, Reddi AH, Lee SJ. Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3. Growth Factors. 1995;12(2):99–109. [PubMed]
  • Massagué J, Attisano L, Wrana JL. The TGF-beta family and its composite receptors. Trends Cell Biol. 1994 May;4(5):172–178. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...