Topological similarities in TGF-beta 2, PDGF-BB and NGF define a superfamily of polypeptide growth factors

Structure. 1993 Oct 15;1(2):153-9. doi: 10.1016/0969-2126(93)90029-g.


Background: The development of functional diversity through gene duplication and subsequent divergent evolution can give rise to proteins that have little or no sequence similarity, but retain similar topologies.

Results: The crystal structures of nerve growth factor, transforming growth factor-beta 2 and platelet-derived growth factor-BB show that all three are based on a cystine-knot plus beta-strands topology. There is very little sequence identity between the three proteins and the relationship between the structures had not been deduced from sequence comparisons. Each growth factor is usually active as a dimer; each exists as a dimer in the crystal, but the relative orientations of the protomers are different in each case.

Conclusion: The structural motif of disulphide bonds and hydrogen-bonded beta-strands unexpectedly found in these three growth factors acts as a stable framework for elaboration of loops of low sequence similarity that contain the specificity for receptor interaction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Becaplermin
  • Computer Graphics
  • Growth Substances / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Growth Factors / chemistry*
  • Platelet-Derived Growth Factor / chemistry*
  • Protein Structure, Secondary*
  • Proto-Oncogene Proteins c-sis
  • Recombinant Proteins / chemistry
  • Software
  • Transforming Growth Factor beta / chemistry*


  • Growth Substances
  • Nerve Growth Factors
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Becaplermin