ArticleProceedings of the National Academy of Sciences of the United States of America2004
Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 94 citations in OpenAlex.
- Genetic variability in thrombopoietin receptor and GATA1 influences response to eltrombopag in dengue-induced thrombocytopenia.Scientific reports · 2026Trial
- EMoMiS: A pipeline for epitope-based molecular mimicry search in protein structures with potential applications to SARS-CoV-2.Computational and structural biotechnology journal · 2026Article
- MPL receptor dimerization and the thrombopoietin pathway in primary immune thrombocytopenia: from molecular mechanisms to targeted therapies.Frontiers in medicine · 2026Review
- Thrombopoietic agents enhance bone healing in mice, rats, and pigs.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Structural basis of MPL activation by thrombopoietin.Blood vessels, thrombosis & hemostasis · 2024Article
- A Rare THPO Gene Mutation in a Saudi Female Child: A Case Report and Literature Review.Cureus · 2024Article
- Thrombopoietin, the Primary Regulator of Platelet Production: From Mythos to Logos, a Thirty-Year Journey.Biomolecules · 2024Review
- Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.Nature communications · 2024Article
- Improving pharmacological activities of thrombopoietin mimetic peptide by genetic fusion to albumin-binding domain.Biotechnology letters · 2023Article
- Review on the Biogenesis of Platelets in Lungs and Its Alterations in SARS-CoV-2 Infection Patients.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2023Review
- Pyrazole-containing pharmaceuticals: target, pharmacological activity, and their SAR studies.RSC medicinal chemistry · 2022Review
- Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins.Viruses · 2022Article
- Thrombopoietin-based CAR-T cells demonstrate in vitro and in vivo cytotoxicity to MPL positive acute myelogenous leukemia and hematopoietic stem cells.Gene therapy · 2022Article
- Development of an Automated Chemiluminescent Enzyme Immunoassay for Measuring Thrombopoietin in Human Plasma.Diagnostics (Basel, Switzerland) · 2022Article
- The thrombopoietin receptor: revisiting the master regulator of platelet production.Platelets · 2021Review
- Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia.Blood advances · 2020Article
- Article
- Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim.EMBO molecular medicine · 2018Article
- Normal and pathological dynamics of platelets in humans.Journal of mathematical biology · 2017Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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