Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines.
Interleukin 20 (IL-20) is a pleotropic IL-10 family cytokine that protects epithelial surfaces from pathogens. However, dysregulated IL-20 signaling is implicated in several human pathologies including psoriasis, rheumatoid arthritis, atherosclerosis, and osteoporosis. IL-20, and related cytokines IL-19 and IL-24, designated IL-20 subfamily cytokines (IL-20SFCs), induce cellular responses through an IL-20R1/IL-20R2 (type I) receptor heterodimer, whereas IL-20 and IL-24 also signal through the IL-22R1/IL-20R2 (type II) receptor complex. The crystal structure of the IL-20/IL-20R1/IL-20R2 complex reveals how type I and II complexes discriminate cognate from noncognate ligands. The structure also defines how the receptor-cytokine interfaces are affinity tuned to allow distinct signaling through a receptor complex shared by three different ligands. Our results provide unique insights into the complexity of IL-20SFC signaling that may be critical in the design of mechanistic-based inhibitors of IL-20SFC-mediated inflammatory disease.
Center for Biophysical Sciences, University of Alabama, Birmingham, AL 35294, USA.
Naomi J
NJ
Logsdon
Ashlesha
A
Deshpande
Bethany D
BD
Harris
Kanagalaghatta R
KR
Rajashankar
Mark R
MR
Walter
D001172:Arthritis, Rheumatoid / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D007378:Interleukins / Q000737:chemistry* / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization / Q000502:physiology; D020836:Protein Structure, Quaternary; D011565:Psoriasis / Q000378:metabolism; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000099180:Interleukin-24
D007378:Interleukins; D018123:Receptors, Interleukin; D000099180:Interleukin-24; C421250:IL19 protein, human; C492510:interleukin-20 receptor; C422042:interleukin 20