Insights into the structure of hepatocyte growth factor/scatter factor (HGF/SF) and implications for receptor activation

FEBS Lett. 1998 Jun 23;430(1-2):126-9. doi: 10.1016/s0014-5793(98)00558-4.


The modular structure of HGF/SF offers a reductionist or 'divide and rule' approach to the analysis of structure and function. Domain deletion experiments have established that the N domain, kringle 1 and kringle 2 are essential for HGF/SF activity and that truncated variants containing the N domain and kringle 1 (NK1) or kringles 1 and 2 (NK2) can exhibit partial agonistic or antagonistic activity depending on target cells. Comparative modelling has been used to predict the 3D structures of the six domains of HGF/SF. More recently, NMR methods have shown that the N domain has a novel fold, the charge distribution of which suggests a heparin binding site. Crystals of NK1 indicate the relationship of this domain to the kringle 1, offering further insights into the mechanism of domain interactions and receptor activation.

Publication types

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

MeSH terms

  • Binding Sites
  • Enzyme Activation
  • Heparin / metabolism*
  • Hepatocyte Growth Factor / chemistry*
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Conformation*
  • Proto-Oncogene Proteins c-met / metabolism*


  • Hepatocyte Growth Factor
  • Heparin
  • Proto-Oncogene Proteins c-met