| First Author | Verstraete K | Year | 2014 |
| Journal | Nat Struct Mol Biol | Volume | 21 |
| Issue | 4 | Pages | 375-82 |
| PubMed ID | 24632570 | Mgi Jnum | J:245289 |
| Mgi Id | MGI:5916195 | Doi | 10.1038/nsmb.2794 |
| Citation | Verstraete K, et al. (2014) Structural basis of the proinflammatory signaling complex mediated by TSLP. Nat Struct Mol Biol 21(4):375-82 |
| abstractText | 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. |
