PMID- 11076027 OWN - NLM STAT- MEDLINE DCOM- 20010621 LR - 20051116 IS - 1431-6730 (Print) IS - 1431-6730 (Linking) VI - 381 IP - 9-10 DP - 2000 Sep-Oct TI - Protein-protein interactions in receptor activation and intracellular signalling. PG - 955-9 AB - 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 GPry, 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 A2, such as Cdk6INK4 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 betagamma subunits (Gtbetagamma) of the heterotrimeric G protein transducin. FAU - Blundell, T L AU - Blundell TL AD - Department of Biochemistry, University of Cambridge, UK. FAU - Burke, D F AU - Burke DF FAU - Chirgadze, D AU - Chirgadze D FAU - Dhanaraj, V AU - Dhanaraj V FAU - Hyvonen, M AU - Hyvonen M FAU - Innis, C A AU - Innis CA FAU - Parisini, E AU - Parisini E FAU - Pellegrini, L AU - Pellegrini L FAU - Sayed, M AU - Sayed M FAU - Sibanda, B L AU - Sibanda BL LA - eng SI - PDB/1BET PT - Journal Article PT - Review PL - Germany TA - Biol Chem JT - Biological chemistry JID - 9700112 RN - 0 (Proteins) RN - 0 (Receptors, Cell Surface) SB - IM MH - Animals MH - Biotransformation MH - Cell Communication/*physiology MH - Humans MH - Proteins/chemistry/*physiology MH - Receptors, Cell Surface/*physiology MH - Signal Transduction/*physiology RF - 18 EDAT- 2000/11/15 11:00 MHDA- 2001/06/22 10:01 CRDT- 2000/11/15 11:00 PHST- 2000/11/15 11:00 [pubmed] PHST- 2001/06/22 10:01 [medline] PHST- 2000/11/15 11:00 [entrez] AID - 10.1515/BC.2000.117 [doi] PST - ppublish SO - Biol Chem. 2000 Sep-Oct;381(9-10):955-9. doi: 10.1515/BC.2000.117.