4NN7

Cytokine receptor complex - Crystal form 2

Summary for 4NN7

• Entry DOI: 10.2210/pdb4nn7/pdb
• Related: 4NN5 4NN6
• Descriptor: Thymic stromal lymphopoietin, Interleukin-7 receptor subunit alpha, Cytokine receptor-like factor 2 (3 entities in total)
• Functional Keywords: four helical bundle fold, chr domains, tslp cytokine signaling, tslpr and il-7ralpha receptors, cell surface, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• Biological source: Mus musculus (mouse); More
• Cellular location: Secreted : Q9JIE6; Membrane; Single-pass type I membrane protein: P16872; Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 3: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: Q8CII9
• Total number of polymer chains: 3
• Total formula weight: 63354.11

Authors

Verstraete, K.,van Schie, L.,Savvides, S.N. (deposition date: 2013-11-16, release date: 2014-03-19, Last modification date: 2023-09-20)

Primary citation

Verstraete, K.,van Schie, L.,Vyncke, L.,Bloch, Y.,Tavernier, J.,Pauwels, E.,Peelman, F.,Savvides, S.N.
Structural basis of the proinflammatory signaling complex mediated by TSLP.
Nat.Struct.Mol.Biol., 21:375-382, 2014

PubMed Abstract: 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 α-chain (IL-7Rα) to evoke membrane-proximal receptor-receptor contacts poised for intracellular signaling. Binding of TSLP to TSLPR is a mechanistic prerequisite for recruitment of IL-7Rα 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-7Rα and establish a consensus for the geometry of ternary complexes mediated by interleukin 2 (IL-2)-family cytokines.

PubMed: 24632570
DOI: 10.1038/nsmb.2794

Experimental method

X-RAY DIFFRACTION (3.775 Å)