Structural highlights
4nn7 is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Related: | 4nn5, 4nn6 |
| Gene: | Tslp (LK3 transgenic mice), Il7r, IL7RA (LK3 transgenic mice), Crlf2, CRLF2 (TSLPR), Crlm2, Tpte2, Tslpr (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[TSLP_MOUSE] Cytokine that induces the release of T-cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly activating mast cells (By similarity). [CRLF2_MOUSE] Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2. Implicated in the development of the hematopoietic system. [IL7RA_MOUSE] Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).
Publication Abstract from PubMed
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.
Structural basis of the proinflammatory signaling complex mediated by TSLP.,Verstraete K, van Schie L, Vyncke L, Bloch Y, Tavernier J, Pauwels E, Peelman F, Savvides SN Nat Struct Mol Biol. 2014 Mar 16. doi: 10.1038/nsmb.2794. PMID:24632570[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Verstraete K, van Schie L, Vyncke L, Bloch Y, Tavernier J, Pauwels E, Peelman F, Savvides SN. Structural basis of the proinflammatory signaling complex mediated by TSLP. Nat Struct Mol Biol. 2014 Mar 16. doi: 10.1038/nsmb.2794. PMID:24632570 doi:http://dx.doi.org/10.1038/nsmb.2794
