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1ktz
From Proteopedia
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(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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Revision as of 15:48, 12 November 2007
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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
Page seeded by OCA on Mon Nov 12 17:54:46 2007
