6KN9

Crystal structure of human interleukin 18 receptor beta extracellular domain in complex with an antagonistic scFv

Summary for 6KN9

• Entry DOI: 10.2210/pdb6kn9/pdb
• Descriptor: Interleukin-18 receptor accessory protein, scFv, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: interleukin receptor, antibody, complex, antagonist, cytokine
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 198098.10

Authors

Wu, D.H.,Liu, C.C. (deposition date: 2019-08-05, release date: 2020-02-12, Last modification date: 2024-11-13)

Primary citation

Liu, S.,Miersch, S.,Li, P.,Bai, B.X,,Liu, C.C.,Qin, W.M.,Su, J.,Huang, H.M.,Pan, J.,Sidhu, S.S.,Wu, D.H.
A Synthetic Human Antibody Antagonizes IL-18R beta Signaling Through an Allosteric Mechanism.
J.Mol.Biol., 432:1169-1182, 2020

PubMed Abstract: The interleukin-18 subfamily belongs to the interleukin-1 family and plays an important role in modulating innate and adaptive immune responses. Dysregulation of IL-18 has been implicated in or correlated with numerous diseases, including inflammatory diseases, autoimmune disorders, and cancer. Thus, blockade of IL-18 signaling may offer therapeutic benefits in many pathological settings. Here, we report the development of synthetic human antibodies that target human IL-18Rβ and block IL-18-mediated IFN-γ secretion by inhibiting NF-κB and MAPK dependent pathways. The crystal structure of a potent antagonist antibody in complex with IL-18Rβ revealed inhibition through an unexpected allosteric mechanism. Our findings offer a novel means for therapeutic intervention in the IL-18 pathway and may provide a new strategy for targeting cytokine receptors.

PubMed: 31954129
DOI: 10.1016/j.jmb.2020.01.012

Experimental method

X-RAY DIFFRACTION (3.302 Å)