7zg0

Murine IL-27 in complex with IL-27Ra and a non-competing Nb

spinqualitylabelsall models 7zg0, resolution 3.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7zg0 is a 8 chain structure with sequence from Lama glama 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 3.18Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Interleukin-27 (IL-27) uniquely assembles p28 and EBI3 subunits to a heterodimeric cytokine that signals via IL-27Ralpha and gp130. To provide the structural framework for receptor activation by IL-27 and its emerging therapeutic targeting, we report here crystal structures of mouse IL-27 in complex with IL-27Ralpha and of human IL-27 in complex with SRF388, a monoclonal antibody undergoing clinical trials with oncology indications. One face of the helical p28 subunit interacts with EBI3, while the opposite face nestles into the interdomain elbow of IL-27Ralpha to juxtapose IL-27Ralpha to EBI3. This orients IL-27Ralpha for paired signaling with gp130, which only uses its immunoglobulin domain to bind to IL-27. Such a signaling complex is distinct from those mediated by IL-12 and IL-23. The SRF388 binding epitope on IL-27 overlaps with the IL-27Ralpha interaction site explaining its potent antagonistic properties. Collectively, our findings will facilitate the mechanistic interrogation, engineering, and therapeutic targeting of IL-27. Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27.,Skladanowska K, Bloch Y, Strand J, White KF, Hua J, Aldridge D, Welin M, Logan DT, Soete A, Merceron R, Murphy C, Provost M, Bazan JF, Hunter CA, Hill JA, Savvides SN Cell Rep. 2022 Oct 18;41(3):111490. doi: 10.1016/j.celrep.2022.111490. PMID:36261006 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin 3D structures

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