TI  - Crystal structure of the  <prot>type-I <prot>interleukin-1</prot> receptor</prot>  complexed with
       <prot>interleukin-1beta</prot> .
PG  - 190-4
AB  - <prot>Interleukin-1</prot> (<prot>IL-1</prot>) is an important mediator of inflammatory disease. The
      <prot>IL-1</prot> family currently consists of two agonists, <prot>IL-1alpha</prot> and <prot>IL-1beta</prot>,
      and one antagonist, <prot>IL-1ra</prot>. Each of these molecules binds to the <prot>type I
      <prot>IL-1</prot> receptor</prot> (<prot>IL1R</prot>). The binding of  <prot>IL-1alpha</prot>  or  <prot>IL-1beta</prot>  to   <prot>IL1R</prot>   is an
      early step in <prot>IL-1</prot> 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  <prot>IL-1beta</prot>  bound to the
      extracellular domain of  <prot>IL1R</prot> (<prot>s-IL1R</prot>)  at 2.5 A resolution.  <prot>IL-1beta</prot>  binds
      to  <prot>s-IL1R</prot>  with a 1:1 stoichiometry. The crystal structure shows that
       <prot>s-IL1R</prot>  consists of three immunoglobulin-like domains which wrap around
       <prot>IL-1beta</prot>  in a manner distinct from the structures of previously described
      cytokine-receptor complexes. The two receptor-binding regions on <prot>IL-1beta</prot>
      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.
AD  - Amgen Inc., Boulder, Colorado 80301, USA.
