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

FEBS Letters

Gherardi, Ermanno²  Blundell, Tom L¹  Byrd, R.Andrew³  Chirgadze, Dimitri Y¹  Sowdhamini, R¹  Hepple, Jonathan² 

[1] Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK;Growth Factors Group, Department of Oncology, MRC Center, Hills Road, Cambridge CB2 2QH, UK;Macromolecular NMR Section, ABL-Basic Research Program, NCI-Frederick, Cancer Research and Development Center, Frederick, MD 21702-1201, USA

关键词: Hepatocyte growth factor/scatter factor;    Protein domain;    NMR;    X-ray analysis;    Receptor activation;   

DOI  :  10.1016/S0014-5793(98)00558-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown