IL-6 Type Cytokine Receptor Complexes: Hexamer, Tetramer or Both?
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J. Grötzinger
Abstract
The typical protein fold of most cytokines is a bundle of four antiparallel helices. This ‘four-helical bundle fold’ seems to be unique to cytokines and has not been detected in other proteins. Cytokine receptors, however, can be classified as a subfamily of the immunoglobulin superfamily. Cytokines using the same receptor subunits are grouped into cytokine families. The interleukin-6 (IL-6) type cytokine family comprises six members. IL-6 type cytokines may interact with three receptor subunits instead of the usual two subunits. A tetramer would be the simplest model to describe such a receptor complex, but present orthodoxy describes the active complexes of IL-6 and ciliary neurotrophic factor (CNTF) as hexamers. Here, we summarize the structural and biochemical information on IL-6 type cytokines and discuss interactions between cytokine and individual receptor subunits at alternative positions. Contradictory results regarding the stoichiometry and assembly of signaling receptor complexes are rationalized by a new, unique model. The model stipulates that a ligand-induced transition from an active tetrameric to an inactive hexameric complex serves as a molecular switch that turns off cytokine signals in the presence of supraoptimal cytokine concentrations.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Paul Nurse Felix Hoppe-Seyler Lecturer 1999
- Cyclin Dependent Kinases and Regulation of the Fission Yeast Cell Cycle
- Paper of the Year 1998
- Autonomous Regulation in Mammalian Mitochondrial DNA Transcription
- Prospects for the Precise Engineering of Plant Genomes by Homologous Recombination
- The Glycosphingolipidoses from Disease to Basic Principles of Metabolism
- The Dual Role of Lipopolysaccharide as Effector and Target Molecule
- A Unified Mechanism of Enzymatic Synthesis of Two Calcium Messengers: Cyclic ADP-Ribose and NAADP
- The Tranquilizing Injection of Yersinia Proteins: A Pathogens Strategy to Resist Host Defense
- IL-6 Type Cytokine Receptor Complexes: Hexamer, Tetramer or Both?
- Genetically Engineered and Synthetic Allergen Derivatives: Candidates for Vaccination against Type I Allergy
- Molecular Farming of Recombinant Antibodies in Plants
- Chimeric Restriction Enzymes: What Is Next?
- Viroids with Hammerhead Ribozymes: Some Unique Structural and Functional Aspects with Respect to Other Members of the Group
- Mutagenesis via Insertional or Restriction Enzyme-Mediated Integration (REMI) as a Tool to Tag Pathogenicity Related Genes in Plant Pathogenic Fungi
- Role of Mitochondria in Parkinson Disease
- Mitochondria Harbouring Mutant mtDNA a Cuckoo in the Nest?
- Mutant p53: Gain-of-Function Oncoproteins and Wild-Type p53 Inactivators
- The Role of Chemokines in Cutaneous Allergic Inflammation
- Mutations of Calcium Channel beta Subunit Genes in Mice
- Agonist-Stimulated Pathways of Calcium Signaling in Pancreatic Acinar Cells
- Some of the Early Events Underlying Th2. Cell Maturation and Susceptibility to Leishmania major Infection in BALB/c Mice
- Universal and Unique Features of Kinesin Motors: Insights from a Comparison of Fungal and Animal Conventional Kinesins
- Elementary Steps in Protein Folding
- Molecular Reaction Mechanisms of Proteins Monitored by Time-Resolved FTIR-Spectroscopy
- Sugars as Signal Molecules in Plant Seed Development
- Diphosphoinositol Polyphosphates: The Final Frontier for Inositide Research?
- A Role of Poly (ADP-Ribose) Polymerase in NF- B Transcriptional Activation
- Processing of Artificial Peptide-DNA-Conjugates by the Mitochondrial Intermediate Peptidase (MIP)
- The Two SH2-Domain-Containing Inositol 5-Phosphatases SHIP1 and SHIP2 Are Coexpressed in Human T Lymphocytes
- Differential Distribution of Four Hyperpolarization-Activated Cation Channels in Mouse Brain
- The Structure of the Nucleotide-Binding Site of Kinesin
- Atomic Resolution Crystal Structure of Hydroxynitrile Lyase from <I>Hevea brasiliensis</I>
- Comparative Modeling of Amoebapores and Granulysin Based on the NK-Lysin Structure Structural and Functional Implications
- A Nonspecific, Single-Stranded Nuclease Activity with Characteristics of a Topoisomerase Found in a Major Grass Pollen Allergen: Possible Biological Significance
- Functional Characterisation of Dictyostelium Myosin II with Conserved Tryptophanyl Residue 501 Mutated to Tyrosine
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- Directed Evolution of an Esterase from Pseudomonas fluorescens. Random Mutagenesis by Error-Prone PCR or a Mutator Strain and Identification of Mutants Showing Enhanced Enantioselectivity by a Resorufin-Based Fluorescence Assay