Title : Charged
residues dominate a unique interlocking topography in the heterodimeric cytokine
interleukin-12
Abstract :
- Human interleukin-12 ( IL-12 , p70 ) is an early pro-inflammatory cytokine, comprising two disulfide-linked subunits , p35 and p40
- We solved the crystal structures of monomeric human p40 at 2.5 A and the human p70 complex at 2.8 A resolution, which reveals that IL-12 is similar to class 1 cytokine-receptor complexes
- They also include the first description of an N-terminal immunoglobulin-like domain , found on the p40 subunit
- Several charged residues from p35 and p40 intercalate to form a unique interlocking topography, shown by mutagenesis to be critical for p70 formation
- A central arginine residue from p35 projects into a deep pocket on p40 , which may be an ideal target for a small molecule antagonist of IL-12 formation