Title : Crystal structure of the entire
ectodomain of
gp130 : insights into the molecular assembly of the tall cytokine
receptor complexes
Abstract :
- gp130 is the shared signal-transducing receptor subunit for the large and important family of interleukin 6-like cytokines
- Previous x-ray structures of ligand- receptor complexes of this family lack the three membrane-proximal domains that are essential for signal transduction
- Here we report the crystal structure of the entire extracellular portion of human gp130 ( domains 1-6, D1-D6 D1-D6 ) at 3 .6 A resolution, in an unliganded form, as well as a higher resolution structure of the membrane-proximal fibronectin type III domains ( D4-D6 D4-D6 ) at 1.9 A
- This represents the first atomic resolution structure of the complete ectodomain of any "tall" cytokine receptor
- These structures show that other than a reorientation of the D1 domain , there is little structural change in gp130 upon ligand binding
- They also reveal that the interface between the D4 and D5 domains forms an acute bend in the gp130 structure
- Key residues at this interface are highly conserved across the entire tall receptor family, suggesting that this acute bend may be a common feature of these receptors
- Importantly, this geometry positions the C termini of the membrane-proximal fibronectin type III domains of the tall cytokine receptors in close proximity within the transmembrane complex, favorable for receptor-associated Janus kinases to trans-phosphorylate and activate each other