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Tom L. Blundell, David F. Burke, Dimitri Chirgadze, Venugopal Dhanaraj, Marko Hyvönen, C. Axel Innis, Emilio Parisini, Luca Pellegrini, Muhammed Sayed, B. Lynn Sibanda
Protein-Protein Interactions in Receptor Activation and Intracellular Signalling
We review here signalling complexes that we have defined using X-ray analysis in our laboratory. They include growth factors and their receptors: nerve growth factor (NGF) and its hetero-hexameric 7S NGF storage complex, hepatocyte growth factor/scatter factor (HGF/SF) NK1 dimers and fibroblast growth factor (FGF1) in complex with its receptor (FGFR2) ectodomain and heparin. We also review our recent structural studies on intracellular signalling complexes, focusing on phosducin transducin G??, CK2 protein kinase and its complexes, and the cyclin D-dependent kinase, Cdk6, bound to the cell cycle inhibitor p19INK4d. Comparing the structures of these complexes with others we show that the surface area buried in signalling interactions does not always give a good indication of the strength of the interactions. We show that conformational changes are often important in complexes with intermediate buried surface areas of 1500 to 2000 ?2, such as Cdk6 INK4 interactions. Some interactions involve recognition of continuous epitopes, where there is no necessity for a tertiary structure and very often the binding conformation is induced during the process of interaction, for example phosducin binding to the ?? subunits (Gt??) of the heterotrimeric G protein transducin.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 381, 09/2000
Pages: 955 - 959