8U18
Cryo-EM structure of murine Thrombopoietin receptor ectodomain in complex with Tpo
Summary for 8U18
| Entry DOI | 10.2210/pdb8u18/pdb |
| EMDB information | 41805 |
| Descriptor | Thrombopoietin receptor,GCN4 isoform 1, Thrombopoietin, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | receptor, cytokine, signalling, haematopoiesis, cytokine-receptor complex, cytokine/receptor |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 3 |
| Total formula weight | 135149.25 |
| Authors | Sarson-Lawrence, K.S.,Hardy, J.M.,Leis, A.,Babon, J.J.,Kershaw, N.J. (deposition date: 2023-08-30, release date: 2024-02-07, Last modification date: 2024-10-16) |
| Primary citation | Sarson-Lawrence, K.T.G.,Hardy, J.M.,Iaria, J.,Stockwell, D.,Behrens, K.,Saiyed, T.,Tan, C.,Jebeli, L.,Scott, N.E.,Dite, T.A.,Nicola, N.A.,Leis, A.P.,Babon, J.J.,Kershaw, N.J. Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin. Nat Commun, 15:1135-1135, 2024 Cited by PubMed Abstract: 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. PubMed: 38326297DOI: 10.1038/s41467-024-45356-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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