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.
Department of Biochemistry, University of Cambridge, UK.
D Y
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Chirgadze
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Hepple
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Byrd
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Sowdhamini
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Blundell
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Gherardi
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