Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12.
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Yoon C, Johnston SC, Tang J, Stahl M, Tobin JF, Somers WS
Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12.
EMBO J. 2000 Jul 17;19(14):3530-41.
- PubMed ID
- 10899108 [ View in PubMed]
- 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.