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Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin‐12
Author(s) -
Yoon Christina,
Johnston Steven C.,
Tang Jin,
Stahl Mark,
Tobin James F.,
Somers William S.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.14.3530
Subject(s) - biology , cytokine , protein subunit , mutagenesis , ternary complex , arginine , microbiology and biotechnology , biophysics , biochemistry , amino acid , genetics , mutation , enzyme , gene
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 Å and the human p70 complex at 2.8 Å 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.