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Science 291 (5511): 2150-2155

Copyright © 2001 by the American Association for the Advancement of Science

Structure of an Extracellular gp130 Cytokine Receptor Signaling Complex

Dar-chone Chow,1 Xiao-lin He,1 Andrew L. Snow,1 Stefan Rose-John,2 K. Christopher Garcia1*

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.

1 Department of Microbiology and Immunology and Department of Structural Biology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305, USA.
2 Department of Biochemistry, Christian-Albrechts-Universität zu Kiel, Olshausenstrabeta e 40, D-24098 Kiel, Germany.
*   To whom correspondence should be addressed. E-mail: kcgarcia{at}stanford.edu


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