6h41

Structure of the complex of the IL-5 inhibitory peptide AF17121 bound to the IL-5 receptor IL-5Ralpha

spinqualitylabelsall models 6h41, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6h41 is a 2 chain structure with sequence from Homo sapiens 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 2.75Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Interleukin-5 (IL-5) is a T-helper cell of subtype 2 cytokine involved in many aspects of eosinophil life. Eosinophilic granulocytes play a pathogenic role in the progression of atopic diseases, such as allergy, asthma and atopic dermatitis and hypereosinophilic syndromes. Here, eosinophils upon activation degranulate leading to the release of proinflammatory proteins and mediators stored in intracellular vesicles termed granula thereby causing local inflammation, which when persisting leads to tissue damage and organ failure. As a key regulator of eosinophil function, IL-5 therefore presents a major pharmaceutical target and approaches to interfere with IL-5 receptor activation are of great interest. Here we present the structure of the IL-5 inhibiting peptide AF17121 bound to the extracellular domain of the IL-5 receptor IL-5Ralpha. The small 18mer cyclic peptide snugly fits into the wrench-like cleft of the IL-5 receptor, thereby blocking access of key residues for IL-5 binding. While AF17121 and IL-5 seemingly bind to a similar epitope at IL-5Ralpha, functional studies show that recognition and binding of both ligands differ. Using the structure data, peptide variants with improved IL-5 inhibition have been generated, which might present valuable starting points for superior peptide-based IL-5 antagonists. Structural Basis of Interleukin-5 Inhibition by the Small Cyclic Peptide AF17121.,Scheide-Noeth JP, Rosen M, Baumstark D, Dietz H, Mueller TD J Mol Biol. 2018 Dec 7. pii: S0022-2836(18)31271-3. doi:, 10.1016/j.jmb.2018.11.029. PMID:30529748 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin receptor 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA