1KTZ : Crystal Structure of the Human TGF-beta Type II Receptor Extracellular Domain in Complex with TGF-beta3

  • Cynthia S. Hinck (Contributor)
  • Andrew P. Hinck (University of Pittsburgh) (Contributor)
  • P. John Hart (Contributor)
  • Shashank Deep (Contributor)
  • Alexander Bryan Taylor (Contributor)
  • Zhanyong Shu (Contributor)



Experimental Technique/Method:X-RAY DIFFRACTION
Release Date:2002-02-27
Deposition Date:2002-01-18
Revision Date:2008-04-27#2011-07-13
Molecular Weight:26588.14
Macromolecule Type:Protein
Residue Count:234
Atom Site Count:1493

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.
Date made available2002

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