TI  - Characterization of the receptor binding sites of human <prot>leukemia
      inhibitory factor</prot> and creation of antagonists.
PG  - 11971-8
AB  - Residues in   human <prot>leukemia inhibitory factor</prot> (<prot>hLIF</prot>)   crucial for binding to
      both the  human <prot>LIF receptor</prot> (R)  and  <prot>gp130</prot>  were identified by analysis of
      alanine scanning mutants of <prot>hLIF</prot> in assays for both receptor binding and
      bioactivity. The region of  <prot>hLIF</prot>  most important for binding to the  <prot>hLIF-R</prot> 
      is composed of residues from the amino terminus of the D-helix, carboxyl
      terminus of the B-helix, and C-D loop. This site forms a distinct surface
      at the end of the four-helix bundle in the tertiary structure of the
      closely related murine <prot>LIF</prot>. The two residues of  <prot>hLIF</prot>  that contribute the
      majority of free energy for  <prot>hLIF-R</prot>  binding, Phe-156 and Lys-159 are
      surrounded by other residues which have only a moderate impact. This
      arrangement of a few key residues surrounded by less important ones is
      analogous to the functional binding epitope of <prot>human growth hormone</prot> for
      its receptor. A second region of  <prot>hLIF</prot>  that includes residues from the
      carboxyl terminus of the D-helix and A-B loop also had a weak influence on
       <prot>hLIF-R</prot>  binding. Residues in  <prot>hLIF</prot>  from both the A- and C-helices are
      involved in binding the  <prot>gp130</prot> co-receptor . Abolition of the <prot>gp130</prot> binding
      site in <prot>hLIF</prot> created antagonists of <prot>LIF</prot> action.
AD  - CRC Growth Factor Group, Department of Biochemistry, University of Oxford,
