Chapter 2. Bone Morphogenetic Proteins

  1. Prof. Dr. Edmund Bäuerlein
  1. Walter Sebald,
  2. Oachim Nickel,
  3. Axel Seher and
  4. Thomas D. Müller

Published Online: 20 MAR 2008

DOI: 10.1002/9783527619443.ch46

Handbook of Biomineralization: Biological Aspects and Structure Formation

Handbook of Biomineralization: Biological Aspects and Structure Formation

How to Cite

Sebald, W., Nickel, O., Seher, A. and Müller, T. D. (2007) Bone Morphogenetic Proteins, in Handbook of Biomineralization: Biological Aspects and Structure Formation (ed E. Bäuerlein), Wiley-VCH Verlag GmbH, Weinheim, Germany. doi: 10.1002/9783527619443.ch46

Editor Information

  1. Max-Planck-Institute for Biochemistry, Department of Membrane Biochemistry, Am Klopferspitz 18 A, 82152 Planegg, Germany

Publication History

  1. Published Online: 20 MAR 2008
  2. Published Print: 25 MAY 2007

ISBN Information

Print ISBN: 9783527316410

Online ISBN: 9783527619443

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Keywords:

  • bone morphogenetic protein (BMP);
  • growth and differentiation factor (GDF);
  • TGF-β superfamily;
  • BMP receptor;
  • x-ray structure;
  • BMP signaling;
  • bone formation and repair;
  • mutants and variants

Summary

Bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs) determine multiple processes in early embryonic development and orga-nogenesis, including the formation of the bones and joints of the axial and appendicular skeleton. BMP-2 and BMP-7 (which is also known as OP-1) are approved as drugs and medical devices for the treatment of non-union fractures and for spinal fusion. Possible future indications for BMPs, GDFs or variants of these proteins include osteoporosis, osteoarthritis, fibrosis, parodontosis, and sinus lift. BMPs and GDFs are members of the TGF-β superfamily which signal into the cell by using two types of single-span membrane receptor chains that both have a cytosolic serine/threonine protein kinase domain. The extracellular ligand-binding domains are small, rich in disulfide bonds, and their fold is related to the three-finger toxins as, for example, are some of the conotoxins. The crystal structure of binary and ternary complexes between BMPs and the ectodo-mains of type I and type II receptors reveals the mechanism of receptor activation and the important determinants (hot spots) for binding specificity and affinity. Structure-based design of BMP and GDF variants yields proteins with new and potentially useful properties.