Abstract
Leukemia inhibitory factor (LIF) receptor is a cell surface receptor that mediates the actions of LIF and other IL-6 type cytokines through the formation of high-affinity signaling complexes with gp130. Here we present the crystal structure of a complex of mouse LIF receptor with human LIF at 4.0 A resolution. The structure is, to date, the largest cytokine receptor fragment determined by x-ray crystallography. The binding of LIF to its receptor via the central Ig-like domain is unlike other cytokine receptor complexes that bind ligand predominantly through their cytokine-binding modules. This structure, in combination with previous crystallographic studies, also provides a structural template to understand the formation and orientation of the high-affinity signaling complex between LIF, LIF receptor, and gp130.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Crystallography, X-Ray
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Cytokine Receptor gp130 / chemistry
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Cytokine Receptor gp130 / metabolism
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Humans
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Immunoglobulins / chemistry*
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Immunoglobulins / genetics
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Immunoglobulins / immunology
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Immunoglobulins / metabolism*
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Interleukin-6 / chemistry
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Interleukin-6 / metabolism
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Leukemia Inhibitory Factor / chemistry*
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Leukemia Inhibitory Factor / genetics
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Leukemia Inhibitory Factor / immunology
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Leukemia Inhibitory Factor / metabolism*
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Ligands
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Mice
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Models, Molecular
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Protein Binding
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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Receptors, OSM-LIF / chemistry*
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Receptors, OSM-LIF / genetics
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Receptors, OSM-LIF / immunology
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Receptors, OSM-LIF / metabolism*
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Signal Transduction
Substances
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Immunoglobulins
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Interleukin-6
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LIF protein, human
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Leukemia Inhibitory Factor
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Ligands
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Receptors, OSM-LIF
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Cytokine Receptor gp130