TI  - A new cytokine-receptor binding mode revealed by the crystal structure of
      the <prot><prot>IL-1</prot> receptor</prot> with an antagonist.
PG  - 194-200
AB  - Inflammation, regardless of whether it is provoked by infection or by
      tissue damage, starts with the activation of macrophages which initiate a
      cascade of inflammatory responses by producing the cytokines <prot>interleukin-1</prot>
      (<prot>IL-1</prot>) and <prot>tumour necrosis factor-alpha</prot> (ref. 1). Three naturally
      occurring ligands for the    <prot><prot>IL-1</prot> receptor</prot> (<prot>IL1R</prot>)    exist: the agonists
       <prot>IL-1alpha</prot>  and  <prot>IL-1beta</prot>  and the  <prot><prot><prot>IL-1</prot>-receptor</prot> antagonist</prot> <prot>IL1RA</prot>  (ref. 2).
      <prot>IL-1</prot> is the only cytokine for which a naturally occurring antagonist is
      known. Here we describe the crystal structure at 2.7 A resolution of the
      soluble extracellular part of  <prot>type-I <prot>IL1R</prot></prot>  complexed with  <prot>IL1RA</prot> . The
      receptor consists of three immunoglobulin-like domains. Domains 1 and 2
      are tightly linked, but domain three is completely separate and connected
      by a flexible linker. Residues of all three domains contact the antagonist
      and include the five critical <prot>IL1RA</prot> residues which were identified by
      site-directed mutagenesis. A region that is important for biological
      function in <prot>IL-1beta</prot>, the 'receptor trigger site' is not in direct contact
      with the receptor in the <prot>IL1RA</prot> complex. Modelling studies suggest that
      this <prot>IL-1beta</prot> trigger site might induce a movement of domain 3.
AD  - Marion Merrell Dow Research Institute, Strasbourg, France.
