Convergent Mechanisms for Recognition of Divergent Cytokines by the Shared Signaling Receptor gp130

Gp130 is a shared cell-surface signaling receptor for at least ten different hematopoietic cytokines, but the basis of its degenerate recognition properties is unknown. We have determined the crystal structure of human leukemia inhibitory factor (LIF) bound to the cytokine binding region (CHR) of gp...

Full description

Saved in:
Bibliographic Details
Published in:Molecular cell 2003-09, Vol.12 (3), p.577-589
Main Authors: Boulanger, Martin J, Bankovich, Alexander J, Kortemme, Tanja, Baker, David, Garcia, K.Christopher
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - chemistry
Antigens, CD - immunology
Binding Sites - immunology
Cells, Cultured
Cross Reactions - immunology
Crystallography, X-Ray
Cytokine Receptor gp130
Cytokines - immunology
Eukaryotic Cells - immunology
Eukaryotic Cells - metabolism
Growth Inhibitors - chemistry
Growth Inhibitors - immunology
Immunity, Cellular - immunology
Insecta
Interleukin-6
Leukemia Inhibitory Factor
Lymphokines - chemistry
Lymphokines - immunology
Macromolecular Substances
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - immunology
Models, Molecular
Molecular Structure
Protein Binding - immunology
Protein Structure, Tertiary - physiology
Receptors, Cell Surface - chemistry
Receptors, Cell Surface - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gp130 is a shared cell-surface signaling receptor for at least ten different hematopoietic cytokines, but the basis of its degenerate recognition properties is unknown. We have determined the crystal structure of human leukemia inhibitory factor (LIF) bound to the cytokine binding region (CHR) of gp130 at 2.5 Å resolution. Strikingly, we find that the shared binding site on gp130 has an entirely rigid core, while the LIF binding interface diverges sharply in structure and chemistry from that of other gp130 ligands. Dissection of the LIF-gp130 interface, along with comparative studies of other gp130 cytokines, reveal that gp130 has evolved a “thermodynamic plasticity” that is relatively insensitive to ligand structure, to enable crossreactivity. These observations reveal a novel and alternative mechanism for degenerate recognition from that of structural plasticity.
ISSN:1097-2765
1097-4164
DOI:10.1016/S1097-2765(03)00365-4