| First Author | Hart PJ | Year | 2002 |
| Journal | Nat Struct Biol | Volume | 9 |
| Issue | 3 | Pages | 203-8 |
| PubMed ID | 11850637 | Mgi Jnum | J:74997 |
| Mgi Id | MGI:2159532 | Doi | 10.1038/nsb766 |
| Citation | Hart PJ, et al. (2002) Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex. Nat Struct Biol 9(3):203-8 |
| abstractText | 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. |
