6lvx

Crystal structure of TLR7/Cpd-1 (SM-374527) complex

spinqualitylabelsall models 6lvx, resolution 2.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.77Å Ligands: EWL, NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent TLR7 agonists, we develop a series of TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography and cryo-electron microscopy, we identify the open conformation of the receptor and reveal the structural equilibrium between open and closed conformations that underlies TLR7 antagonism, as well as the detailed mechanism by which TLR7-specific antagonists bind to their binding pocket in TLR7. Our work provides small-molecule TLR7-specific antagonists and suggests the TLR7-targeting strategy for treating autoimmune diseases. Structural analysis reveals TLR7 dynamics underlying antagonism.,Tojo S, Zhang Z, Matsui H, Tahara M, Ikeguchi M, Kochi M, Kamada M, Shigematsu H, Tsutsumi A, Adachi N, Shibata T, Yamamoto M, Kikkawa M, Senda T, Isobe Y, Ohto U, Shimizu T Nat Commun. 2020 Oct 15;11(1):5204. doi: 10.1038/s41467-020-19025-z. PMID:33060576 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Toll-like Receptor 3D structures

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