2PJY

Structural basis for cooperative assembly of the TGF-beta signaling complex

Summary for 2PJY

• Entry DOI: 10.2210/pdb2pjy/pdb
• Descriptor: Transforming growth factor beta-3, TGF-beta receptor type-2, TGF-beta receptor type-1, ... (4 entities in total)
• Functional Keywords: ternary complex, three finger toxin, 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 P36897
• Total number of polymer chains: 3
• Total formula weight: 33694.56

Authors

Groppe, J.,Zubieta, C. (deposition date: 2007-04-16, release date: 2008-02-05, Last modification date: 2024-11-20)

Primary citation

Groppe, J.,Hinck, C.S.,Samavarchi-Tehrani, P.,Zubieta, C.,Schuermann, J.P.,Taylor, A.B.,Schwarz, P.M.,Wrana, J.L.,Hinck, A.P.
Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding.
Mol.Cell, 29:157-168, 2008

PubMed Abstract: Dimeric ligands of the transforming growth factor-beta (TGF-beta) superfamily signal across cell membranes in a distinctive manner by assembling heterotetrameric complexes of structurally related serine/threonine-kinase receptor pairs. Unlike complexes of the bone morphogenetic protein (BMP) branch that apparently form due to avidity from membrane localization, TGF-beta complexes assemble cooperatively through recruitment of the low-affinity (type I) receptor by the ligand-bound high-affinity (type II) pair. Here we report the crystal structure of TGF-beta3 in complex with the extracellular domains of both pairs of receptors, revealing that the type I docks and becomes tethered via unique extensions at a composite ligand-type II interface. Disrupting the receptor-receptor interactions conferred by these extensions abolishes assembly of the signaling complex and signal transduction (Smad activation). Although structurally similar, BMP and TGF-beta receptors bind in dramatically different modes, mediating graded and switch-like assembly mechanisms that may have coevolved with branch-specific groups of cytoplasmic effectors.

PubMed: 18243111
DOI: 10.1016/j.molcel.2007.11.039

Experimental method

X-RAY DIFFRACTION (3 Å)