8u18

Cryo-EM structure of murine Thrombopoietin receptor ectodomain in complex with Tpo

spinqualitylabelsall models 8u18, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8u18 is a 3 chain structure with sequence from Mus musculus and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.6Å Ligands: BMA, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Thrombopoietin (Tpo) is the primary regulator of megakaryocyte and platelet numbers and is required for haematopoetic stem cell maintenance. Tpo functions by binding its receptor (TpoR, a homodimeric Class I cytokine receptor) and initiating cell proliferation or differentiation. Here we characterise the murine Tpo:TpoR signalling complex biochemically and structurally, using cryo-electron microscopy. Tpo uses opposing surfaces to recruit two copies of receptor, forming a 1:2 complex. Although it binds to the same, membrane-distal site on both receptor chains, it does so with significantly different affinities and its highly glycosylated C-terminal domain is not required. In one receptor chain, a large insertion, unique to TpoR, forms a partially structured loop that contacts cytokine. Tpo binding induces the juxtaposition of the two receptor chains adjacent to the cell membrane. The therapeutic agent romiplostim also targets the cytokine-binding site and the characterisation presented here supports the future development of improved TpoR agonists. Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.,Sarson-Lawrence KTG, Hardy JM, Iaria J, Stockwell D, Behrens K, Saiyed T, Tan C, Jebeli L, Scott NE, Dite TA, Nicola NA, Leis AP, Babon JJ, Kershaw NJ Nat Commun. 2024 Feb 7;15(1):1135. doi: 10.1038/s41467-024-45356-2. PMID:38326297 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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