Structural basis of receptor sharing by interleukin 17 cytokines.
Interleukin 17 (IL-17)-producing helper T cells (T(H)-17 cells), together with their effector cytokines, including members of the IL-17 family, are emerging as key mediators of chronic inflammatory and autoimmune disorders. Here we present the crystal structure of a complex of IL-17 receptor A (IL-17RA) bound to IL-17F in a 1:2 stoichiometry. The mechanism of complex formation was unique for cytokines and involved the engagement of IL-17 by two fibronectin-type domains of IL-17RA in a groove between the IL-17 homodimer interface. Binding of the first receptor to the IL-17 cytokines modulated the affinity and specificity of the second receptor-binding event, thereby promoting heterodimeric versus homodimeric complex formation. IL-17RA used a common recognition strategy to bind to several members of the IL-17 family, which allows it to potentially act as a shared receptor in multiple different signaling complexes.
Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, USA.
Lauren K
LK
Ely
Suzanne
S
Fischer
K Christopher
KC
Garcia
D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D020381:Interleukin-17 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D053722:Receptors, Interleukin-17 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D016415:Sequence Alignment
D020381:Interleukin-17; D053722:Receptors, Interleukin-17