TI  - <prot>BMP-2</prot> antagonists emerge from alterations in the low-affinity binding
      epitope for receptor <prot>BMPR-II</prot>.
PG  - 3314-24
AB  - <prot>Bone morphogenetic protein-2</prot> (<prot>BMP-2</prot>) induces bone formation and
      regeneration in adult vertebrates and regulates important developmental
      processes in all animals. <prot>BMP-2</prot> is a homodimeric cysteine knot protein
      that, as a member of the <prot>transforming growth factor-beta</prot> (<prot>TGF-beta</prot>)
      superfamily, signals by oligomerizing type I and type II receptor
      serine-kinases in the cell membrane. The binding epitopes of   <prot>BMP-2</prot>   for
       <prot>BMPR-IA</prot> (type I) and  <prot>BMPR-II</prot> or <prot>ActR-II</prot> (type II)  were characterized using
      <prot>BMP-2</prot> mutant proteins for analysis of interactions with receptor
      ectodomains. A large epitope 1 for high-affinity <prot>BMPR-IA</prot> binding was
      detected spanning the interface of the   <prot>BMP-2</prot>   dimer. A smaller epitope 2
      for the low-affinity binding of <prot>BMPR-II</prot> was found to be assembled by
      determinants of a single monomer. Symmetry-related pairs of the two
      juxtaposed epitopes occur near the <prot>BMP-2</prot> poles. Mutations in both epitopes
      yielded variants with reduced biological activity in C2C12 cells; however,
      only epitope 2 variants behaved as antagonists partially or completely
      inhibiting <prot>BMP-2</prot> activity. These findings provide a framework for the
      molecular description of receptor recognition and activation in the
      BMP/<prot>TGF-beta</prot> superfamily.
AD  - Lehrstuhl fur Physiologische Chemie II, Theodor-Boveri-Institut fur
