8f60

anti-BTLA monoclonal antibody r23C8 in complex with BTLA

spinqualitylabelsall models 8f60, resolution 1.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8f60 is a 3 chain structure with sequence from Homo sapiens and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.64Å Ligands: ACT, BMA, MAN, NAG, PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BTLA_HUMAN Lymphocyte inhibitory receptor which inhibits lymphocytes during immune response. Publication Abstract from PubMed B and T lymphocyte attenuator (BTLA) is an attractive target for a new class of therapeutics that attempt to rebalance the immune system by agonizing checkpoint inhibitory receptors (CIRs). Herpesvirus entry mediator (HVEM) binds BTLA in both trans- and cis-orientations. We report here the development and structural characterization of three humanized BTLA agonist antibodies, 22B3, 25F7, and 23C8. We determined the crystal structures of the antibody-BTLA complexes, showing that these antibodies bind distinct and non-overlapping epitopes of BTLA. While all three antibodies activate BTLA, 22B3 mimics HVEM binding to BTLA and shows the strongest agonistic activity in functional cell assays and in an imiquimod-induced mouse model of psoriasis. 22B3 is also capable of modulating HVEM signaling through the BTLA-HVEM cis-interaction. The data obtained from crystal structures, biochemical assays, and functional studies provide a mechanistic model of HVEM and BTLA organization on the cell surface and informed the discovery of a highly active BTLA agonist. Epitope topography of agonist antibodies to the checkpoint inhibitory receptor BTLA.,Cheung TC, Atwell S, Bafetti L, Cuenca PD, Froning K, Hendle J, Hickey M, Ho C, Huang J, Lieu R, Lim S, Lippner D, Obungu V, Ward-Kavanagh L, Weichert K, Ware CF, Vendel AC Structure. 2023 Aug 3;31(8):958-967.e3. doi: 10.1016/j.str.2023.05.011. Epub 2023 , Jun 5. PMID:37279757 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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