Structure of an extracellular gp130 cytokine receptor signaling complex

D. C. Chow, X. L. He, A. L. Snow, S. Rose-John, K. Christopher Garcia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

216 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2150-2155
Number of pages6
JournalScience
Volume291
Issue number5511
DOIs
StatePublished - Mar 16 2001

ASJC Scopus subject areas

  • General

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