4NN6: Cytokine receptor complex - Crystal form 1B

Thymic stromal lymphopoietin (TSLP), a cytokine produced by epithelial cells at barrier surfaces, is pivotal for the development of widespread chronic inflammatory disorders such as asthma and atopic dermatitis. The structure of the mouse TSLP-mediated signaling complex reveals how TSLP establishes extensive interfaces with its cognate receptor (TSLPR) and the shared interleukin 7 receptor alpha-chain (IL-7Ralpha) to evoke membrane-proximal receptor-receptor contacts poised for intracellular signaling. Binding of TSLP to TSLPR is a mechanistic prerequisite for recruitment of IL-7Ralpha to the high-affinity ternary complex, which we propose is coupled to a structural switch in TSLP at the crossroads of the cytokine-receptor interfaces. Functional interrogation of TSLP-receptor interfaces points to putative interaction hotspots that could be exploited for antagonist design. Finally, we derive the structural rationale for the functional duality of IL-7Ralpha and establish a consensus for the geometry of ternary complexes mediated by interleukin 2 (IL-2)-family cytokines.
PDB ID: 4NN6Download
MMDB ID: 118460
PDB Deposition Date: 2013/11/16
Updated in MMDB: 2018/07
Experimental Method:
x-ray diffraction
Resolution: 2.545  Å
Source Organism:
Similar Structures:
Biological Unit for 4NN6: trimeric; determined by author
Molecular Components in 4NN6
Label Count Molecule
Proteins (3 molecules)
Thymic Stromal Lymphopoietin(Gene symbol: Tslp)
Molecule annotation
Interleukin-7 Receptor Subunit Alpha(Gene symbol: Il7r)
Molecule annotation
Cytokine Receptor-like Factor 2(Gene symbol: Crlf2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB