1v7n

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[[Image:1v7n.gif|left|200px]]
 
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{{Structure
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==Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab==
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|PDB= 1v7n |SIZE=350|CAPTION= <scene name='initialview01'>1v7n</scene>, resolution 3.30&Aring;
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<StructureSection load='1v7n' size='340' side='right'caption='[[1v7n]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1v7n]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V7N FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
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|GENE=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1v7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v7n OCA], [https://pdbe.org/1v7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v7n RCSB], [https://www.ebi.ac.uk/pdbsum/1v7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v7n ProSAT]</span></td></tr>
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}}
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</table>
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== Disease ==
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'''Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab'''
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[https://www.uniprot.org/uniprot/TPO_HUMAN TPO_HUMAN] Defects in THPO are the cause of thrombocythemia type 1 (THCYT1) [MIM:[https://omim.org/entry/187950 187950]. A myeloproliferative disorder characterized by elevated platelet levels due to sustained proliferation of megakaryocytes, and frequently lead to thrombotic and haemorrhagic complications.<ref>PMID:9425899</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/TPO_HUMAN TPO_HUMAN] Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.
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==Overview==
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v7/1v7n_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1v7n ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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.
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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==Disease==
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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. 2004 Feb 17;101(7):1816-21. Epub 2004 Feb 9. PMID:14769915<ref>PMID:14769915</ref>
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Known diseases associated with this structure: Thrombocythemia, essential OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600044 600044]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1V7N is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V7N OCA].
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</div>
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<div class="pdbe-citations 1v7n" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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. 2004 Feb 17;101(7):1816-21. Epub 2004 Feb 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14769915 14769915]
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Feese MD]]
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[[Category: Feese, M D.]]
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[[Category: Hirose M]]
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[[Category: Hirose, M.]]
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[[Category: Kato T]]
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[[Category: Kato, T.]]
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[[Category: Kato Y]]
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[[Category: Kato, Y.]]
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[[Category: Kuroki R]]
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[[Category: Kuroki, R.]]
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[[Category: Maeda Y]]
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[[Category: Maeda, Y.]]
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[[Category: Matsukura Y]]
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[[Category: Matsukura, Y.]]
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[[Category: Miyazaki H]]
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[[Category: Miyazaki, H.]]
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[[Category: Shigematsu H]]
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[[Category: Shigematsu, H.]]
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[[Category: Tamada T]]
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[[Category: Tamada, T.]]
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[[Category: complex (cytokine/antibody)]]
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[[Category: fab fragment]]
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[[Category: thrombopoietin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:41:52 2008''
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Current revision

Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab

PDB ID 1v7n

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