6lyc

Crystal structure of the NOD SIRPa complex with D4-2

spinqualitylabelsall models 6lyc, resolution 1.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6lyc is a 2 chain structure with sequence from Mus musculus 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 1.36Å Ligands: ACE, ACY, DTY, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Medium-sized macrocyclic peptides are an alternative to small compounds and large biomolecules as a class of pharmaceutics. The CD47-SIRPalpha signaling axis functions as an innate immune checkpoint that inhibits phagocytosis in phagocytes and has been implicated as a promising target for cancer immunotherapy. The potential of macrocyclic peptides that target this signaling axis as immunotherapeutic agents has remained unknown, however. Here we have developed a macrocyclic peptide consisting of 15 amino acids that binds to the ectodomain of mouse SIRPalpha and efficiently blocks its interaction with CD47 in an allosteric manner. The peptide markedly promoted the phagocytosis of antibody-opsonized tumor cells by macrophages in vitro as well as enhanced the inhibitory effect of anti-CD20 or anti-gp75 antibodies on tumor formation or metastasis in vivo. Our results suggest that allosteric inhibition of the CD47-SIRPalpha interaction by macrocyclic peptides is a potential approach to cancer immunotherapy. Macrocyclic Peptide-Mediated Blockade of the CD47-SIRPalpha Interaction as a Potential Cancer Immunotherapy.,Hazama D, Yin Y, Murata Y, Matsuda M, Okamoto T, Tanaka D, Terasaka N, Zhao J, Sakamoto M, Kakuchi Y, Saito Y, Kotani T, Nishimura Y, Nakagawa A, Suga H, Matozaki T Cell Chem Biol. 2020 Sep 17;27(9):1181-1191.e7. doi:, 10.1016/j.chembiol.2020.06.008. Epub 2020 Jul 7. PMID:32640189 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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