Structures of an ActRIIB:activin a complex reveal a novel binding mode for TGF-β ligand:receptor interactions

Thomas B. Thompson, Teresa K. Woodruff, Theodore S. Jardetzky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

The TGF-β superfamily of ligands and receptors stimulate cellular events in diverse processes ranging from cell late specification in development to immune suppression. Activins define a major subgroup of TGF-β ligands that regulate cellular differentiation, proliferation, activation and apoptosis. Activins signal through complexes formed with type I and type II serine/threonine kinase receptors. We have solved the crystal structure of activin A bound to the extracellular domain of a type II receptor, ActRIIB, revealing the details of this interaction. ActRIIB binds to the outer edges of the activin finger regions, with the two receptors juxtaposed in close proximity, in a mode that differs from TGF-β3 binding to type II receptors. The dimeric activin A structure differs from other known TGF-β ligand structures, adopting a compact folded-back conformation. The crystal structure of the complex is consistent with recruitment of two type I receptors into a close packed arrangement at the cell surface and suggests that diversity in the conformational arrangements of TGF-β ligand dimers could influence cellular signaling processes.

Original languageEnglish (US)
Pages (from-to)1555-1566
Number of pages12
JournalEMBO Journal
Volume22
Issue number7
DOIs
StatePublished - Apr 1 2003

Keywords

  • ActRIIB
  • Activin
  • Receptors
  • Signaling
  • Structure
  • TGF-β

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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