1ktz

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spinqualitylabelsall models 1ktz, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of the Human TGF-beta Type II Receptor Extracellular Domain in Complex with TGF-beta3

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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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