Insights into the structure of hepatocyte growth factor/scatter factor (HGF/SF) and implications for receptor activation.
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.
Chirgadze
D Y
DY
Department of Biochemistry, University of Cambridge, UK.
Hepple
J
J
Byrd
R A
RA
Sowdhamini
R
R
Blundell
T L
TL
Gherardi
E
E
D001665:Binding Sites; D004789:Enzyme Activation; D006493:Heparin / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*
D017228:Hepatocyte Growth Factor; D006493:Heparin; D019859:Proto-Oncogene Proteins c-met