7S2S
nanobody bound to Interleukin-2Rbeta
Summary for 7S2S
| Entry DOI | 10.2210/pdb7s2s/pdb |
| Descriptor | IL2Rb-binding nanobody, Interleukin-2 receptor subunit beta, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | nanobody, protein binding, cytokine receptor |
| Biological source | Camelus bactrianus More |
| Total number of polymer chains | 4 |
| Total formula weight | 88265.99 |
| Authors | Glassman, C.R.,Jude, K.M.,Yen, M.,Garcia, K.C. (deposition date: 2021-09-03, release date: 2022-03-30, Last modification date: 2023-10-18) |
| Primary citation | Yen, M.,Ren, J.,Liu, Q.,Glassman, C.R.,Sheahan, T.P.,Picton, L.K.,Moreira, F.R.,Rustagi, A.,Jude, K.M.,Zhao, X.,Blish, C.A.,Baric, R.S.,Su, L.L.,Garcia, K.C. Facile discovery of surrogate cytokine agonists. Cell, 185:1414-, 2022 Cited by PubMed Abstract: Cytokines are powerful immune modulators that initiate signaling through receptor dimerization, but natural cytokines have structural limitations as therapeutics. We present a strategy to discover cytokine surrogate agonists by using modular ligands that exploit induced proximity and receptor dimer geometry as pharmacological metrics amenable to high-throughput screening. Using VHH and scFv to human interleukin-2/15, type-I interferon, and interleukin-10 receptors, we generated combinatorial matrices of single-chain bispecific ligands that exhibited diverse spectrums of functional activities, including potent inhibition of SARS-CoV-2 by surrogate interferons. Crystal structures of IL-2R:VHH complexes revealed that variation in receptor dimer geometries resulted in functionally diverse signaling outputs. This modular platform enabled engineering of surrogate ligands that compelled assembly of an IL-2R/IL-10R heterodimer, which does not naturally exist, that signaled through pSTAT5 on T and natural killer (NK) cells. This "cytokine med-chem" approach, rooted in principles of induced proximity, is generalizable for discovery of diversified agonists for many ligand-receptor systems. PubMed: 35325595DOI: 10.1016/j.cell.2022.02.025 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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