Structure of an extracellular gp130 cytokine receptor signaling complex.
The activation of gp130, a shared signal-transducing receptor for a family of cytokines, is initiated by recognition of ligand followed by oligomerization into a higher order signaling complex. Kaposi's sarcoma-associated herpesvirus encodes a functional homolog of human interleukin-6 (IL-6) that activates human gp130. In the 2.4 angstrom crystal structure of the extracellular signaling assembly between viral IL-6 and human gp130, two complexes are cross-linked into a tetramer through direct interactions between the immunoglobulin domain of gp130 and site III of viral IL-6, which is necessary for receptor activation. Unlike human IL-6 (which uses many hydrophilic residues), the viral cytokine largely uses hydrophobic amino acids to contact gp130, which enhances the complementarity of the viral IL-6-gp130 binding interfaces. The cross-reactivity of gp130 is apparently due to a chemical plasticity evident in the amphipathic gp130 cytokine-binding sites.
Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305, USA.
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D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D050822:Cytokine Receptor gp130; D000939:Epitopes; D006801:Humans; D006860:Hydrogen Bonding; D015850:Interleukin-6 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D018716:Molecular Mimicry; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014764:Viral Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D000939:Epitopes; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D014764:Viral Proteins; D050822:Cytokine Receptor gp130