1v7m
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The cytokine thrombopoietin (TPO), the ligand for the hematopoietic | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Feese, M | + | [[Category: Feese, M D.]] |
[[Category: Hirose, M.]] | [[Category: Hirose, M.]] | ||
[[Category: Kato, T.]] | [[Category: Kato, T.]] | ||
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[[Category: thrombopoietin]] | [[Category: thrombopoietin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:32:18 2008'' |
Revision as of 13:32, 21 February 2008
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Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Thrombocythemia, essential OMIM:[600044]
About this Structure
1V7M is a Single protein structure of sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
Reference
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. 2004 Feb 17;101(7):1816-21. Epub 2004 Feb 9. PMID:14769915
Page seeded by OCA on Thu Feb 21 15:32:18 2008
