1v7m

From Proteopedia

(Difference between revisions)

Revision as of 07:49, 25 October 2023

Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab

Structural highlights

1v7m is a 6 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.51Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TPO_HUMAN Defects in THPO are the cause of thrombocythemia type 1 (THCYT1) [MIM:187950. A myeloproliferative disorder characterized by elevated platelet levels due to sustained proliferation of megakaryocytes, and frequently lead to thrombotic and haemorrhagic complications.^[1]

Function

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC. An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet. 1998 Jan;18(1):49-52. PMID:9425899 doi:10.1038/ng0198-49
↑ 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. Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1816-21. Epub 2004 Feb 9. PMID:14769915 doi:http://dx.doi.org/10.1073/pnas.0308530100

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1v7m"

@@ Line 3: / Line 3: @@
 <StructureSection load='1v7m' size='340' side='right'caption='[[1v7m]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1v7m]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V7M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1v7m]] is a 6 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=1V7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V7M FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1v7n|1v7n]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.51&#8491;</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1v7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v7m OCA], [https://pdbe.org/1v7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v7m RCSB], [https://www.ebi.ac.uk/pdbsum/1v7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v7m ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[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>
+[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>
 == Function ==
-[[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.
+[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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Feese, M D]]
+[[Category: Feese MD]]
-[[Category: Hirose, M]]
+[[Category: Hirose M]]
-[[Category: Kato, T]]
+[[Category: Kato T]]
-[[Category: Kato, Y]]
+[[Category: Kato Y]]
-[[Category: Kuroki, R]]
+[[Category: Kuroki R]]
-[[Category: Maeda, Y]]
+[[Category: Maeda Y]]
-[[Category: Matsukura, Y]]
+[[Category: Matsukura Y]]
-[[Category: Miyazaki, H]]
+[[Category: Miyazaki H]]
-[[Category: Shigematsu, H]]
+[[Category: Shigematsu H]]
-[[Category: Tamada, T]]
+[[Category: Tamada T]]
-[[Category: Fab fragment]]
-[[Category: Immune system-cytokine complex]]
-[[Category: Thrombopoietin]]

1v7m

From Proteopedia

Revision as of 07:49, 25 October 2023

Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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