1KTZ

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

Summary for 1KTZ

• Entry DOI: 10.2210/pdb1ktz/pdb
• Descriptor: TRANSFORMING GROWTH FACTOR BETA 3, TGF-beta Type II Receptor (3 entities in total)
• Functional Keywords: cytokine-receptor complex, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P10600; Membrane; Single-pass type I membrane protein: P37173
• Total number of polymer chains: 2
• Total formula weight: 26588.14

Authors

Hart, P.J.,Deep, S.,Taylor, A.B.,Shu, Z.,Hinck, C.S.,Hinck, A.P. (deposition date: 2002-01-18, release date: 2002-02-27, Last modification date: 2024-10-09)

Primary citation

Hart, P.J.,Deep, S.,Taylor, A.B.,Shu, Z.,Hinck, C.S.,Hinck, A.P.
Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex.
Nat.Struct.Biol., 9:203-208, 2002

PubMed Abstract: 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.

PubMed: 11850637

Experimental method

X-RAY DIFFRACTION (2.15 Å)