1v7m: Difference between revisions
New page: left|200px<br /> <applet load="1v7m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1v7m, resolution 2.51Å" /> '''Human Thrombopoieti... |
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[[Image:1v7m. | [[Image:1v7m.jpg|left|200px]]<br /><applet load="1v7m" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1v7m, resolution 2.51Å" /> | caption="1v7m, resolution 2.51Å" /> | ||
'''Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab'''<br /> | '''Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1V7M is a [http://en.wikipedia.org/wiki/Single_protein 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:// | 1V7M is a [http://en.wikipedia.org/wiki/Single_protein 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=1V7M OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thrombopoietin]] | [[Category: thrombopoietin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:04:35 2008'' | ||
Revision as of 18:04, 15 February 2008
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Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Thrombocythemia, essential OMIM:[600044]
About this StructureAbout this Structure
1V7M is a Single protein structure of sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
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
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