CRYSTAL STRUCTURE OF HUMAN INTERLEUKIN-10 AT 1.6 Å RESOLUTION. Alexander Zdanov, Celine Schalk-Hihi, Alexander Wlodawer, Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research and Development Center, ABL-Basic Research Program, Frederick, Maryland, 21702

Interleukin-10 (IL-10) is a cytokine that inhibits production of a number of regulatory factors. The molecule is a homodimer of two intepenetrating monomers (160 amino acid residues each), forming a V-shaped structure. Each half of the structure consists of six [[alpha]]-helices, four originating from one monomer and two from the other. The overal topology of the IL-10 bears close resemblance to interferon [[gamma]].

The crystal structure of human interleukin-10 (IL-10) has been refined at 1.6 Å resolution against X-ray diffraction data collected at 100 K with the use of synchrotron radiation. Although similar to the IL-10 structure determined previously at room temperature, the low-temperature structure contains, in addition, four N-terminal residues, three sulfate anions, and 175 extra water molecules. Whereas the main-chain conformation is preserved, about 30% of the side chains, most of them on the protein surface, assume different conformations, and the protein itself appears to contract slightly at low temperature.

A computer model of a complex of IL-10 with its two soluble domains of its receptor has been generated based on the topological similarity of IL-10 to interferon-[[gamma]]. The contact region between the IL-10 and each receptor shows excellent complementarity of polar and hydrophobic interactions, suggesting that the model is generally correct.