1ktz
From Proteopedia
(New page: 200px<br /> <applet load="1ktz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ktz, resolution 2.15Å" /> '''Crystal Structure o...) |
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| - | [[Image:1ktz.gif|left|200px]]<br /> | + | [[Image:1ktz.gif|left|200px]]<br /><applet load="1ktz" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ktz" size=" | + | |
caption="1ktz, resolution 2.15Å" /> | caption="1ktz, resolution 2.15Å" /> | ||
'''Crystal Structure of the Human TGF-beta Type II Receptor Extracellular Domain in Complex with TGF-beta3'''<br /> | '''Crystal Structure of the Human TGF-beta Type II Receptor Extracellular Domain in Complex with TGF-beta3'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Transforming growth factor-beta (TGF-beta) is the prototype of a large | + | Transforming growth factor-beta (TGF-beta) is the prototype of a large family of structurally related cytokines that play key roles in maintaining cellular homeostasis by signaling through two classes of functionally distinct Ser/Thr kinase receptors, designated as type I and type II. TGF-beta initiates receptor assembly by binding with high affinity to the type II receptor. Here, we present the 2.15 A crystal structure of the extracellular ligand-binding domain of the human TGF-beta type II receptor (ecTbetaR2) in complex with human TGF-beta3. ecTbetaR2 interacts with homodimeric TGF-beta3 by binding identical finger segments at opposite ends of the growth factor. Relative to the canonical 'closed' conformation previously observed in ligand structures across the superfamily, ecTbetaR2-bound TGF-beta3 shows an altered arrangement of its monomeric subunits, designated the 'open' conformation. The mode of TGF-beta3 binding shown by ecTbetaR2 is compatible with both ligand conformations. This, in addition to the predicted mode for TGF-beta binding to the type I receptor ectodomain (ecTbetaR1), suggests an assembly mechanism in which ecTbetaR1 and ecTbetaR2 bind at adjacent positions on the ligand surface and directly contact each other via protein--protein interactions. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KTZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | + | 1KTZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Deep, S.]] | [[Category: Deep, S.]] | ||
| - | [[Category: Hart, P | + | [[Category: Hart, P J.]] |
| - | [[Category: Hinck, A | + | [[Category: Hinck, A P.]] |
| - | [[Category: Hinck, C | + | [[Category: Hinck, C S.]] |
[[Category: Shu, Z.]] | [[Category: Shu, Z.]] | ||
| - | [[Category: Taylor, A | + | [[Category: Taylor, A B.]] |
[[Category: cytokine-receptor complex]] | [[Category: cytokine-receptor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:37:53 2008'' |
Revision as of 11:37, 21 February 2008
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Crystal Structure of the Human TGF-beta Type II Receptor Extracellular Domain in Complex with TGF-beta3
Contents |
Overview
Transforming growth factor-beta (TGF-beta) is the prototype of a large family of structurally related cytokines that play key roles in maintaining cellular homeostasis by signaling through two classes of functionally distinct Ser/Thr kinase receptors, designated as type I and type II. TGF-beta initiates receptor assembly by binding with high affinity to the type II receptor. Here, we present the 2.15 A crystal structure of the extracellular ligand-binding domain of the human TGF-beta type II receptor (ecTbetaR2) in complex with human TGF-beta3. ecTbetaR2 interacts with homodimeric TGF-beta3 by binding identical finger segments at opposite ends of the growth factor. Relative to the canonical 'closed' conformation previously observed in ligand structures across the superfamily, ecTbetaR2-bound TGF-beta3 shows an altered arrangement of its monomeric subunits, designated the 'open' conformation. The mode of TGF-beta3 binding shown by ecTbetaR2 is compatible with both ligand conformations. This, in addition to the predicted mode for TGF-beta binding to the type I receptor ectodomain (ecTbetaR1), suggests an assembly mechanism in which ecTbetaR1 and ecTbetaR2 bind at adjacent positions on the ligand surface and directly contact each other via protein--protein interactions.
Disease
Known diseases associated with this structure: Aortic aneurysm, familial thoracic 3 OMIM:[190182], Arrhythmogenic right ventricular dysplasia 1 OMIM:[190230], Colon cancer OMIM:[190182], Colorectal cancer, hereditary nonpolyposis, type 6 OMIM:[190182], Esophageal cancer OMIM:[190182], Loeys-Dietz syndrome OMIM:[190182], Marfan syndrome, type II OMIM:[190182]
About this Structure
1KTZ is a Protein complex structure of sequences from Homo sapiens. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex., Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP, Nat Struct Biol. 2002 Mar;9(3):203-8. PMID:11850637
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