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.
Logsdon
Naomi J
NJ
Department of Microbiology and Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, AL 35294, USA.
Jones
Brandi C
BC
Josephson
Kristopher
K
Cook
Jennifer
J
Walter
Mark R
MR
D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D016753:Interleukin-10 / Q000737:chemistry* / Q000235:genetics; D007378:Interleukins / Q000737:chemistry* / Q000235:genetics; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000235:genetics; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000737:chemistry; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000097043:Interleukin-22
D016753:Interleukin-10; D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D000097043:Interleukin-22; C415369:interleukin-22 receptor