4yqx | pdb_00004yqx

Mouse IL-2 Bound to JES6-1 scFv Fragment

spinqualitylabelsall models 4yqx, resolution 2.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yqx is a 6 chain structure with sequence from Buffalo rat and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FUC, NAG Gene: Il2, Il-2 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IL2_MOUSE] 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 Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates immune cell homeostasis and has been used to treat a range of disorders including cancer and autoimmune disease. IL-2 signals via interleukin-2 receptor-beta (IL-2Rbeta):IL-2Rgamma heterodimers on cells expressing high (regulatory T cells, Treg) or low (effector cells) amounts of IL-2Ralpha (CD25). When complexed with IL-2, certain anti-cytokine antibodies preferentially stimulate expansion of Treg (JES6-1) or effector (S4B6) cells, offering a strategy for targeted disease therapy. We found that JES6-1 sterically blocked the IL-2:IL-2Rbeta and IL-2:IL-2Rgamma interactions, but also allosterically lowered the IL-2:IL-2Ralpha affinity through a "triggered exchange" mechanism favoring IL-2Ralpha(hi) Treg cells, creating a positive feedback loop for IL-2Ralpha(hi) cell activation. Conversely, S4B6 sterically blocked the IL-2:IL-2Ralpha interaction, while also conformationally stabilizing the IL-2:IL-2Rbeta interaction, thus stimulating all IL-2-responsive immune cells, particularly IL-2Rbeta(hi) effector cells. These insights provide a molecular blueprint for engineering selectively potentiating therapeutic antibodies. Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms.,Spangler JB, Tomala J, Luca VC, Jude KM, Dong S, Ring AM, Votavova P, Pepper M, Kovar M, Garcia KC Immunity. 2015 May 19;42(5):815-25. doi: 10.1016/j.immuni.2015.04.015. PMID:25992858 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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