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  • Title: Insights into the structure of hepatocyte growth factor/scatter factor (HGF/SF) and implications for receptor activation.
    Author: Chirgadze DY, Hepple J, Byrd RA, Sowdhamini R, Blundell TL, Gherardi E.
    Journal: FEBS Lett; 1998 Jun 23; 430(1-2):126-9. PubMed ID: 9678607.
    Abstract:
    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.
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