Protein-Protein Interactions in Receptor Activation and Intracellular Signalling
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Tom L. Blundell
Abstract
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 Gβγ, 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 Å2, 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 βγ subunits (Gtβγ) of the heterotrimeric G protein transducin.
Copyright © 2000 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Alexander J. Varshavsky Felix Hoppe-Seyler Lecturer 2000
- The Ubiquitin System and the N-End Rule Pathway
- Paper of the Year 1999: Award to Igor Stagljar
- A Clockwork Organ
- The Transgeneticists Toolbox: Novel Methods for the Targeted Modification of Eukaryotic Genomes
- Interdependence of Filamentous Actin and Microtubules for Asymmetric Cell Division
- Genetic Analysis of Mammalian Cyclin-Dependent Kinases and Their Inhibitors
- Phosphorylcholine Substituents in Nematodes: Structures, Occurrence and Biological Implications
- Selenium in Biology: Facts and Medical Perspectives
- The Role of Se, Mo and Fe in the Structure and Function of Carbon Monoxide Dehydrogenase
- Molecular Basis for Interactions of the DnaK Chaperone with Substrates
- Protein Import: the Hitchhikers Guide into Chloroplasts
- Pathway Analysis and Metabolic Engineering in Corynebacterium glutamicum
- Metabolic Networks: a Signal-Oriented Approach to Cellular Models
- Representing and Analysing Molecular and Cellular Function Using the Computer
- Protein Aggregation and Pathogenesis of Huntingtons Disease: Mechanisms and Correlations
- The Mitochondrial Protein Import Motor
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- Molecular Genetic Analysis of Glucocorticoid Signaling Using the Cre/loxP System
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- Thyroid Hormone Receptors Bind to an Element in the Connexin43 Promoter
- Analysis of the Deubiquitinating Enzymes of the Yeast Saccharomyces cerevisiae
- Helical Tubes of FtsZ from Methanococcus jannaschii
- Surface Topography of Microtubule Walls Decorated with Monomeric and Dimeric Kinesin Constructs
- Histone Deacetylase Activity Is Required for the Induction of the MyoD Muscle Cell Lineage in Xenopus
- The Effect of Heat Shock on 20S/26S Proteasomes
- Sec61p Is the Main Ribosome Receptor in the Endoplasmic Reticulum of Saccharomyces cerevisiae
