The cystine-knot growth-factor superfamily

Annu Rev Biophys Biomol Struct. 1995;24:269-91. doi: 10.1146/


Four recent crystal structures of growth factors--nerve growth factor, transforming growth factor-beta, platelet-derived growth factor, and human chorionic gonadotropin--from four separate superfamilies revealed that these proteins are structurally related and share a common overall topology. These proteins have very little sequence homology, but they all have an unusual arrangement of six cysteines linked to form a "cystine-knot" conformation. The active forms of these proteins are dimers, either homo- or heterodimers. Despite the overall topological similarity between the monomers, the interfaces used to form the dimer are in each case quite different. Because the surfaces used for dimer formation are mostly hydrophobic, the uniqueness of each dimer accounts for the lack of sequence homology and raises questions about the effectiveness of reverse sequence fitting in this kind of structure as a predictor of structural homology.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Becaplermin
  • Chorionic Gonadotropin / chemistry
  • Growth Substances / chemistry*
  • Growth Substances / classification
  • Models, Molecular
  • Nerve Growth Factors / chemistry
  • Platelet-Derived Growth Factor / chemistry
  • Protein Conformation
  • Proto-Oncogene Proteins c-sis
  • Transforming Growth Factor beta / chemistry


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