9eth | pdb_00009eth

Complex structure of IL-36R D1-D2 domain with 36R-P192 and BI655130 Fab

spinqualitylabelsall models 9eth, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9eth is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: 5CW, 6G5, A1H6Z, ACE, BMA, CHG, GOL, MAN, NA, NAG, NH2, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ILRL2_HUMAN Receptor for interleukin-36 (IL36A, IL36B and IL36G). After binding to interleukin-36 associates with the coreceptor IL1RAP to form the interleukin-36 receptor complex which mediates interleukin-36-dependent activation of NF-kappa-B, MAPK and other pathways (By similarity). The IL-36 signaling system is thought to be present in epithelial barriers and to take part in local inflammatory response; it is similar to the IL-1 system. Seems to be involved in skin inflammatory response by induction of the IL-23/IL-17/IL-22 pathway.[UniProtKB:Q9ERS7] Publication Abstract from PubMed Interleukin-36 receptor (IL-36R), belonging to the IL-1 receptor family, is crucial for host defense and tissue repair. Targeting cytokine receptors with low molecular weight (LMW) compounds remains challenging due to their interaction with the large surface area of cytokine. In this study, two encoded library technologies are used to identify LMW molecules binding to IL-36R's extracellular domain. The mRNA-based display technique identifies 36R-P138, a macrocyclic peptide blocking IL-36R signaling. Importantly, its optimized analog (36R-P192) also effectively suppresses expression of marker genes induced by IL-36 in human skin biopsies. DNA encoded libraries (DEL) screening delivers 36R-D481, a high affinity LMW IL-36R binder, effectively inhibiting IL-36 signaling. X-ray crystallography analysis reveals that both the cyclic peptide and DEL-compound bind to the IL-36R's D1 domain, potentially disrupting IL-36 cytokine binding. This study demonstrates that it is possible to target a cytokine receptor within the IL-1 receptor family using a small molecule ( < 1000 Da). Discovery of selective low molecular weight interleukin-36 receptor antagonists by encoded library technologies.,Velcicky J, Cremosnik G, Scheufler C, Meier P, Wirth E, Felber R, Ramage P, Schaefer M, Kaiser C, Lehmann S, Kutil R, Singeisen S, Mueller-Ristig D, Popp S, Cebe R, Lehr P, Kaupmann K, Erbel P, Rohn TA, Giovannoni J, Dumelin CE, Martiny-Baron G Nat Commun. 2025 Feb 15;16(1):1669. doi: 10.1038/s41467-025-56601-7. PMID:39955284 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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