7dr4

Complex of anti-human IL-2 antibody and human IL-2

spinqualitylabelsall models 7dr4, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7dr4 is a 12 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.49Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease IL2_HUMAN Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17. Function IL2_HUMAN Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. Publication Abstract from PubMed Immunotherapy via interleukin-2 (IL-2) mediated activation of anti-tumor immune response is a promising approach for cancer treatment. The multi-potent cytokine, IL-2 has a central role in immune cell activation and homeostasis. Since IL-2 preferentially activates immunosuppressive T regulatory cells by IL-2Ralpha dependent manner, blocking IL-2:IL-2Ralpha interaction is a key to amplify the IL-2 activity in effector T cells toward anti-tumor response. Anti-IL-2 monoclonal antibodies are good candidates to control the IL-2:IL-2Ralpha interaction. In a previous study, we developed a new IL-2Ralpha mimetic antibody, TCB2, and showed that the human IL-2(hIL-2):TCB2 complex can stimulate T effector cells specifically and elicit potent anti-cancer immunotherapeutic effect, especially when administered in combination with immune checkpoint inhibitors. To understand the molecular mechanism, we determined the crystal structure of TCB2-Fab in a complex with hIL-2 at 2.5 A resolution. Our structural analysis reveals that TCB2 binds to the central area of the hIL-2Ralpha binding region on hIL-2, and binding angle and epitope are different from previously known hIL-2Ralpha mimicking antibody NARA1 which recognizes the top part of hIL-2. TCB2 binding to hIL-2 also induces an allosteric effect that increases the affinity for the hetero-dimeric hIL-2 receptor, IL-2R(beta + gamma), on effector T cells. Crystal structure of human interleukin-2 in complex with TCB2, a new antibody-drug candidate with antitumor activity.,Kim J, Lee JY, Park SY, Lee YJ, Kim MS Oncoimmunology. 2021 Mar 16;10(1):1899671. doi: 10.1080/2162402X.2021.1899671. PMID:33796411 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Interleukin 3D structures

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