Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β

Interleukin-1 (IL-1) is an important mediator of inflammatory disease. The IL-1 family currently consists of two agonists, IL-1 alpha and IL-1 beta , and one antagonist, IL-1ra. Each of these molecules binds to the type I IL-1 receptor (IL1R). The binding of IL-1 alpha or IL-1 beta to IL1R is an ear...

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Bibliographic Details
Published in:Nature (London) 1997-03, Vol.386 (6621), p.190-194
Main Authors: Vigers, Guy P. A, Anderson, Lana J, Caffes, Patricia, Brandhuber, Barbara J
Format: Article
Language:English
Subjects:
Analysis of the immune response. Humoral and cellular immunity
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Lymphokines, interleukins ( function, expression)
Regulatory factors and their cellular receptors
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Summary:Interleukin-1 (IL-1) is an important mediator of inflammatory disease. The IL-1 family currently consists of two agonists, IL-1 alpha and IL-1 beta , and one antagonist, IL-1ra. Each of these molecules binds to the type I IL-1 receptor (IL1R). The binding of IL-1 alpha or IL-1 beta to IL1R is an early step in IL-1 signal transduction and blocking this interaction may therefore be a useful target for the development of new drugs. Here we report the three-dimensional structure of IL-1 beta bound to the extracellular domain of IL1R (s-IL1R) at 2.5 angstrom resolution. IL-1 beta binds to s-IL1R with a 1:1 stoichiometry. The crystal structure shows that s-IL1R consists of three immunoglobulin-like domains which wrap around IL-1 beta in a manner distinct from the structures of previously described cytokine-receptor complexes. The two receptor-binding regions on IL-1 beta identified by site-directed mutagenesis both contact the receptor: one binds to the first two domains of the receptor, while the other binds exclusively to the third domain.
ISSN:0028-0836
1476-4687
DOI:10.1038/386190a0