Receptor recognition by gp130 cytokines.
Cytokines of the gp130 family exert their diverse biological effects by formation of stable high affinity transmembrane receptor complexes that are characterized by the presence of the shared transmembrane signalling receptor gp130. Different gp130 ligands form signalling complexes that vary in both composition and stoichiometry. Analysis of the three-dimensional structure of selected ligands and receptor elements indicates that ligands display three topologically conserved receptor recognition epitopes that interact with complementary ligand recognition elements. The composition of the signalling complex and downstream biological responses is defined by the relative affinity of different receptor components for these epitopes. The detailed structure of receptor recognition epitopes indicates that the generation of small molecule cytokine mimetics may be a feasible objective.
Bravo
J
J
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Heath
J K
JK
D015703:Antigens, CD / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry; D006131:Growth Inhibitors / Q000737:chemistry; D019382:Human Growth Hormone / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry; D053605:Leukemia Inhibitory Factor; D008024:Ligands; D008222:Lymphokines / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018121:Receptors, Cytokine / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D016207:Cytokines; D000939:Epitopes; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008024:Ligands; D008222:Lymphokines; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D050822:Cytokine Receptor gp130