4NN6
Cytokine receptor complex - Crystal form 1B
Summary for 4NN6
| Entry DOI | 10.2210/pdb4nn6/pdb |
| Related | 4NN5 4NN7 |
| Descriptor | Thymic stromal lymphopoietin, Interleukin-7 receptor subunit alpha, Cytokine receptor-like factor 2, ... (4 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: 2024-11-20) |
| 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 Cited by 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: 24632570DOI: 10.1038/nsmb.2794 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.545 Å) |
Structure validation
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