Crystal structure of human interleukin-10 at 1.6 A resolution and a model of a complex with its soluble receptor.
The crystal structure of human interleukin-10 (IL-10) was refined at 1.6 A 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, this low-temperature IL-10 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. A computer model of a complex of IL-10 with its two soluble receptors was generated based on the topological similarity of IL-10 to interferon-gamma. The contact region between the cytokine and each receptor shows excellent complementarity of polar and hydrophobic interactions, suggesting that the model is generally correct and should be useful in guiding mutagenesis experiments.
Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, Maryland 21702, USA.
A
A
Zdanov
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C
Schalk-Hihi
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Wlodawer
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D007371:Interferon-gamma / Q000737:chemistry; D016753:Interleukin-10 / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000378:metabolism; D053701:Receptors, Interleukin-10; D016415:Sequence Alignment; D013696:Temperature
D046911:Macromolecular Substances; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D007371:Interferon-gamma