An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor.
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.
Huyton
Trevor
T
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Zhang
Jian-Guo
JG
Luo
Cindy S
CS
Lou
Mei-Zhen
MZ
Hilton
Douglas J
DJ
Nicola
Nicos A
NA
Garrett
Thomas P J
TP
D000818:Animals; D018360:Crystallography, X-Ray; D050822:Cytokine Receptor gp130 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000737:chemistry / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D053606:Receptors, OSM-LIF / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D007136:Immunoglobulins; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008024:Ligands; D053606:Receptors, OSM-LIF; D050822:Cytokine Receptor gp130