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 r ule' approach to the analysis of structure and function. Domain deleti on experiments have established that the N domain, kringle 1 and kring le 2 are essential for HGF/SF activity and that truncated variants con taining the N domain and kringle 1 (NK1) or kringles 1 and 2 (NK2) can exhibit partial agonistic or antagonistic activity depending on targe t cells. Comparative modelling has been used to predict the 3D structu res of the six domains of HGF/SF, More recently, NMR methods have show n that the N domain has a novel fold, the charge distribution of which suggests a heparin binding site. Crystals of NK1 indicate the relatio nship of this domain to the kringle 1, offering further insights into the mechanism of domain interactions and receptor activation. (C) 1998 Federation of European Biochemical Societies.