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Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment.

Feese MD, Tamada T, Kato Y, Maeda Y, Hirose M, Matsukura Y, Shigematsu H, Muto T, Matsumoto A, Watarai H, Ogami K, Tahara T, Kato T, Miyazaki H, Kuroki R
Proc Natl Acad Sci U S A 101 1816-21 (2004)
Cited: 50 times
EuropePMC logo PMID: 14769915

Abstract

The cytokine thrombopoietin (TPO), the ligand for the hematopoietic receptor c-Mpl, acts as a primary regulator of megakaryocytopoiesis and platelet production. We have determined the crystal structure of the receptor-binding domain of human TPO (hTPO(163)) to a 2.5-A resolution by complexation with a neutralizing Fab fragment. The backbone structure of hTPO(163) has an antiparallel four-helix bundle fold. The neutralizing Fab mainly recognizes the C-D crossover loop containing the species invariant residue Q111. Titration calorimetric experiments show that hTPO(163) interacts with soluble c-Mpl containing the extracellular cytokine receptor homology domains with 1:2 stoichiometry with the binding constants of 3.3 x 10(9) M(-1) and 1.1 x 10(6) M(-1). The presence of the neutralizing Fab did not inhibit binding of hTPO(163) to soluble c-Mpl fragments, but the lower-affinity binding disappeared. Together with prior genetic data, these define the structure-function relationships in TPO and the activation scheme of c-Mpl.

Articles - 1v7n mentioned but not cited (8)

  1. Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment. Feese MD, Tamada T, Kato Y, Maeda Y, Hirose M, Matsukura Y, Shigematsu H, Muto T, Matsumoto A, Watarai H, Ogami K, Tahara T, Kato T, Miyazaki H, Kuroki R. Proc Natl Acad Sci U S A 101 1816-1821 (2004)
  2. Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia. Dasouki MJ, Rafi SK, Olm-Shipman AJ, Wilson NR, Abhyankar S, Ganter B, Furness LM, Fang J, Calado RT, Saadi I. Blood 122 3440-3449 (2013)
  3. Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins. Nunez-Castilla J, Stebliankin V, Baral P, Balbin CA, Sobhan M, Cickovski T, Mondal AM, Narasimhan G, Chapagain P, Mathee K, Siltberg-Liberles J. Viruses 14 1415 (2022)
  4. Calcium-Bound S100P Protein Is a Promiscuous Binding Partner of the Four-Helical Cytokines. Kazakov AS, Deryusheva EI, Permyakova ME, Sokolov AS, Rastrygina VA, Uversky VN, Permyakov EA, Permyakov SE. Int J Mol Sci 23 12000 (2022)
  5. Structural basis of the broadly neutralizing anti-interferon-α antibody rontalizumab. Maurer B, Bosanac I, Shia S, Kwong M, Corpuz R, Vandlen R, Schmidt K, Eigenbrot C. Protein Sci 24 1440-1450 (2015)
  6. Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis. Tsutsumi N, Masoumi Z, James SC, Tucker JA, Winkelmann H, Grey W, Picton LK, Moss L, Wilson SC, Caveney NA, Jude KM, Gati C, Piehler J, Hitchcock IS, Garcia KC. Cell 186 4189-4203.e22 (2023)
  7. 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 15 1135 (2024)
  8. An insight into the thermodynamic characteristics of human thrombopoietin complexation with TN1 antibody. Arai S, Shibazaki C, Adachi M, Honjo E, Tamada T, Maeda Y, Tahara T, Kato T, Miyazaki H, Blaber M, Kuroki R. Protein Sci 25 1786-1796 (2016)


Reviews citing this publication (18)

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  2. The biology of thrombopoietin and thrombopoietin receptor agonists. Kuter DJ. Int J Hematol 98 10-23 (2013)
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  13. New treatments for idiopathic thrombocytopenic purpura: rethinking old hypotheses. Arnold DM, Nazi I, Kelton JG. Expert Opin Investig Drugs 18 805-819 (2009)
  14. Review article: pharmacological approaches for the treatment of thrombocytopenia in patients with chronic liver disease and hepatitis C infection. Afdhal NH, McHutchison JG. Aliment Pharmacol Ther 26 Suppl 1 29-39 (2007)
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  17. Review on the Biogenesis of Platelets in Lungs and Its Alterations in SARS-CoV-2 Infection Patients. Nandhini B, Sureshraj Y, Kaviya M, Sangeetha T, Bharathi K, Balamuralikrishnan B, Manikantan P, Arun M, Haripriya KB, Karthika P, Kalidass S, Anand AV. J Renin Angiotensin Aldosterone Syst 2023 7550197 (2023)
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