Comparison of interleukin-22 and interleukin-10 soluble receptor complexes.

Interleukin-22 (IL-22) is a cellular homolog of IL-10 that stimulates the production of acute-phase reactants. IL-22 and IL-10 require different ligand-specific receptor chains (IL-22R and IL-10R1) but share a second receptor chain (IL-10R2) to initiate cellular responses. The quaternary structures and the ability of IL-22 and IL-10 to engage soluble (s) IL-10R1, IL-22R, IL-10R2 receptor chains were analyzed using size exclusion chromatography and surface plasmon resonance techniques. In contrast to IL-10, which is a homodimer, IL-22 is a monomer in solution that forms a 1:1 interaction with sIL-22R. Kinetic binding data reveal sIL-22R and sIL-10R1 exhibit specific nanomolar binding constants for IL-22 (k(on)/k(off) = 14.9 nM) and a monomeric isomer of IL-10 (IL-10M1) (k(on)/k(off) = 0.7 nM), respectively. In contrast, IL-10R2 exhibits essentially no affinity for IL-22 (K(eq) approximately 1 mM) or IL-10M1 (K(eq) approximately 2 mM) alone but displays a substantial increase in affinity for the IL-10/sIL-10R1 (K(eq) approximately 350 microM) and IL-22/sIL-22R (K(eq) approximately 45 microM) complexes. Three-dimensional models of IL-22 and IL-10 receptor complexes suggest two receptor residues (Gly-44 and Arg-96) are largely responsible for the marked differences in ligand affinity observed for sIL-10R1 and sIL-22R vs. sIL-10R2.

[1]  D. Conklin,et al.  Interleukin 20 Discovery, Receptor Identification, and Role in Epidermal Function , 2001, Cell.

[2]  J. Renauld,et al.  Crystallization and synchrotron X-ray diffraction studies of human interleukin-22. , 2002, Acta crystallographica. Section D, Biological crystallography.

[3]  J. Bazan.  Shared architecture of hormone binding domains in type I and II interferon receptors , 1990, Cell.

[4]  P. Mui,et al.  Disulfide bond assignments and secondary structure analysis of human and murine interleukin 10. , 1993, Biochemistry.

[5]  T. L. Nagabhushan,et al.  Crystal structure of interleukin 10 reveals an interferon gamma-like fold. , 1995, Biochemistry.

[6]  M. Ultsch,et al.  Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. , 1992, Science.

[7]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[8]  S. Pestka,et al.  Identification of the Functional Interleukin-22 (IL-22) Receptor Complex , 2001, The Journal of Biological Chemistry.

[9]  S. Narula,et al.  Characterization of Recombinant Extracellular Domain of Human Interleukin-10 Receptor (*) , 1995, The Journal of Biological Chemistry.

[10]  W. Windsor,et al.  Crystal structure of a complex between interferon-γ and its soluble high-affinity receptor , 1995, Nature.

[11]  Rebecca L Rich,et al.  A survey of the year 2002 commercial optical biosensor literature , 2003, Journal of molecular recognition : JMR.

[12]  S. Pestka,et al.  Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10) , 2000, Genes and Immunity.

[13]  Z. Su,et al.  Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression. , 1995, Oncogene.

[14]  S. Narula,et al.  Characterization of interleukin-10 receptors on human and mouse cells. , 1993, The Journal of biological chemistry.

[15]  J. Bazan,et al.  Structural design and molecular evolution of a cytokine receptor superfamily. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[16]  D. Lejeune,et al.  Cutting Edge: STAT Activation By IL-19, IL-20 and mda-7 Through IL-20 Receptor Complexes of Two Types1 , 2001, The Journal of Immunology.

[17]  H. Fickenscher,et al.  Induction of a Novel Cellular Homolog of Interleukin-10, AK155, by Transformation of T Lymphocytes with Herpesvirus Saimiri , 2000, Journal of Virology.

[18]  D. McPherson,et al.  Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1. , 2001, Acta crystallographica. Section D, Biological crystallography.

[19]  S. Pestka,et al.  Other Kinases Can Substitute for Jak2 in Signal Transduction by Interferon-γ* , 1996, The Journal of Biological Chemistry.

[20]  Wei Wu,et al.  Identification and functional characterization of a second chain of the interleukin‐10 receptor complex , 1997, The EMBO journal.

[21]  R. Coffman,et al.  Interleukin-10 and the interleukin-10 receptor. , 2001, Annual review of immunology.

[22]  Jamila Louahed,et al.  Cloning and Characterization of IL-10-Related T Cell-Derived Inducible Factor (IL-TIF), a Novel Cytokine Structurally Related to IL-10 and Inducible by IL-91 , 2000, The Journal of Immunology.

[23]  B. C. Jones,et al.  Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography. , 2002, Structure.

[24]  A Wlodawer,et al.  Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma. , 1995, Structure.

[25]  Zemin Zhang,et al.  Interleukin (IL)-22, a Novel Human Cytokine That Signals through the Interferon Receptor-related Proteins CRF2–4 and IL-22R* , 2000, The Journal of Biological Chemistry.

[26]  N. Logsdon,et al.  Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. , 2001, Immunity.

[27]  A. Gurney,et al.  Acinar cells of the pancreas are a target of interleukin-22. , 2001, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[28]  Collaborative Computational,et al.  The CCP4 suite: programs for protein crystallography. , 1994, Acta crystallographica. Section D, Biological crystallography.

[29]  J. Sack,et al.  CHAIN — A crystallographic modeling program , 1988 .

[30]  Gerard J. Kleywegt,et al.  Storing diffraction data , 1996, Nature.

[31]  Diane Lejeune,et al.  Interleukin-22 (IL-22) Activates the JAK/STAT, ERK, JNK, and p38 MAP Kinase Pathways in a Rat Hepatoma Cell Line , 2002, The Journal of Biological Chemistry.

[32]  S. Kotenko,et al.  Two Distinct Domains Within the N-Terminal Region of Janus Kinase 1 Interact with Cytokine Receptors1 , 2002, The Journal of Immunology.

[33]  T. L. Nagabhushan,et al.  Design and Analysis of an Engineered Human Interleukin-10 Monomer* , 2000, The Journal of Biological Chemistry.

[34]  J. Renauld,et al.  Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.