PDBsum entry 4nn5

Cytokine/cytokine receptor

PDB id: 4nn5

Contents

Protein chains

109 a.a.

197 a.a.

183 a.a.

Ligands

ACT

NAG

Waters ×330

PDB id:

4nn5

Name:

Cytokine/cytokine receptor

Title:

Cytokine receptor complex - crystal form 1a

Structure:

Thymic stromal lymphopoietin. Chain: a. Fragment: unp residues 20-140. Synonym: tslp, thymic stroma-derived lymphopoietin. Engineered: yes. Mutation: yes. Interleukin-7 receptor subunit alpha. Chain: b. Fragment: extracellular domain (unp residues 21-239).

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: tslp. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s gnti-. Gene: il7r, il7ra. Expressed in: escherichia coli.

Resolution:

1.90Å R-factor: 0.171 R-free: 0.201

Authors:

K.Verstraete,L.Van Schie,S.N.Savvides

Key ref:

K.Verstraete et al. (2014). Structural basis of the proinflammatory signaling complex mediated by TSLP. Nat Struct Biol, 21, 375-382. PubMed id: 24632570 DOI: 10.1038/nsmb.2794

Date:

16-Nov-13 Release date: 19-Mar-14

Protein chain

Q9JIE6  (TSLP_MOUSE) -  Thymic stromal lymphopoietin from Mus musculus

Seq: 140 a.a.

Struc: 109 a.a.*

Protein chain

P16872  (IL7RA_MOUSE) -  Interleukin-7 receptor subunit alpha from Mus musculus

Seq: 459 a.a.

Struc: 197 a.a.

Protein chain

Q8CII9  (CRLF2_MOUSE) -  Cytokine receptor-like factor 2 from Mus musculus

Seq: 359 a.a.

Struc: 183 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/nsmb.2794

Nat Struct Biol 21:375-382 (2014)

PubMed id: 24632570

Structural basis of the proinflammatory signaling complex mediated by TSLP.

K.Verstraete, L.van Schie, L.Vyncke, Y.Bloch, J.Tavernier, E.Pauwels, F.Peelman, S.N.Savvides.

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.