Structure of IL-22 bound to its high-affinity IL-22R1 chain.
IL-22 is an IL-10 family cytokine that initiates innate immune responses against bacterial pathogens and contributes to immune disease. IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22R1 also pairs with the IL-20R2 chain to induce IL-20 and IL-24 signaling. To define the molecular basis of these diverse interactions, we have determined the structure of the IL-22/sIL-22R1 complex. The structure, combined with homology modeling and surface plasmon resonance studies, defines the molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses.
Jones
Brandi C
BC
Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Logsdon
Naomi J
NJ
Walter
Mark R
MR
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D016753:Interleukin-10 / Q000737:chemistry / Q000378:metabolism; D053709:Interleukin-10 Receptor alpha Subunit / Q000737:chemistry / Q000378:metabolism; D007378:Interleukins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000502:physiology; D018123:Receptors, Interleukin / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D013379:Substrate Specificity; D000097043:Interleukin-22
D016753:Interleukin-10; D053709:Interleukin-10 Receptor alpha Subunit; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor