Abstract
The gp130-cytokine system has been fertile ground for protein structure-function studies aimed at elucidating the basis of ligand recognition and receptor activation. A number of longstanding questions involve the mechanism of the stepwise assembly of the active signaling complexes, as well as the structure of the gp130-cytokine complexes. It has been clear from functional studies that the paradigm of gp130-cyokine recognition will differ substantially from the classical homo-dimeric systems, typified by human growth hormone (hGH) and its receptor. Recently, a crystal structure of a viral interleukin-6 (vIL-6), complexed with the D1D2D3 domains of the gp130 extracellular domain, has resolved many of these questions, and reconciled much of the functional and mutagenesis data which have existed for a variety of gp130-cytokines. In this review, we discuss the structure of the vIL-6/gp130 complex in some detail and suggest that the geometry of this complex will be a common structural template utilized by other gp130-cytokines, as well as cytokines from distinct signaling systems.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 225-235 |
| Number of pages | 11 |
| Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
| Volume | 1592 |
| Issue number | 3 |
| DOIs | |
| State | Published - Nov 11 2002 |
Funding
The authors acknowledge support from The Cancer Research Institute, American Heart Association, Pew Foundation, California Cancer Research Program, Terman and Rita Allen Foundations, and March of Dimes.
Keywords
- Complex
- Cytokine
- Receptor
- Recognition
- Signaling
- Structure
- X-ray crystallography
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology