Crystal structure of the human TβR2 ectodomain-TGF-β3 complex

P. John Hart, Shashank Deep, Alexander B. Taylor, Zhanyong Shu, Cynthia S. Hinck, Andrew P. Hinck

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β) 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-β initiates receptor assembly by binding with high affinity to the type II receptor. Here, we present the 2.15 Å crystal structure of the extracellular ligand-binding domain of the human TGF-β type II receptor (ecTβR2) in complex with human TGF-β3. ecTβR2 interacts with homodimeric TGF-β3 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, ecTβR2-bound TGF-β3 shows an altered arrangement of its monomeric subunits, designated the 'open' conformation. The mode of TGF-β3 binding shown by ecTβR2 is compatible with both ligand conformations. This, in addition to the predicted mode for TGF-β binding to the type I receptor ectodomain (ecTβR1), suggests an assembly mechanism in which ecTβR1 and ecTβR2 bind at adjacent positions on the ligand surface and directly contact each other via proteinprotein interactions.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalNature Structural Biology
Volume9
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Transforming Growth Factors
Crystal structure
Ligands
Conformations
Growth Factor Receptors
Fingers
Intercellular Signaling Peptides and Proteins
Homeostasis
Phosphotransferases
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Hart, P. J., Deep, S., Taylor, A. B., Shu, Z., Hinck, C. S., & Hinck, A. P. (2002). Crystal structure of the human TβR2 ectodomain-TGF-β3 complex. Nature Structural Biology, 9(3), 203-208. https://doi.org/10.1038/nsb766

Crystal structure of the human TβR2 ectodomain-TGF-β3 complex. / Hart, P. John; Deep, Shashank; Taylor, Alexander B.; Shu, Zhanyong; Hinck, Cynthia S.; Hinck, Andrew P.

In: Nature Structural Biology, Vol. 9, No. 3, 2002, p. 203-208.

Research output: Contribution to journalArticle

Hart, PJ, Deep, S, Taylor, AB, Shu, Z, Hinck, CS & Hinck, AP 2002, 'Crystal structure of the human TβR2 ectodomain-TGF-β3 complex', Nature Structural Biology, vol. 9, no. 3, pp. 203-208. https://doi.org/10.1038/nsb766
Hart, P. John ; Deep, Shashank ; Taylor, Alexander B. ; Shu, Zhanyong ; Hinck, Cynthia S. ; Hinck, Andrew P. / Crystal structure of the human TβR2 ectodomain-TGF-β3 complex. In: Nature Structural Biology. 2002 ; Vol. 9, No. 3. pp. 203-208.
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