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.
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References
Holgate, S.T. Innate and adaptive immune responses in asthma. Nat. Med. 18, 673–683 (2012).
Decramer, M., Janssens, W. & Miravitlles, M. Chronic obstructive pulmonary disease. Lancet 379, 1341–1351 (2012).
Schmitt, J. et al. Assessment of clinical signs of atopic dermatitis: a systematic review and recommendation. J. Allergy Clin. Immunol. 132, 1337–1347 (2013).
Abonia, J.P. & Rothenberg, M.E. Eosinophilic esophagitis: rapidly advancing insights. Annu. Rev. Med. 63, 421–434 (2012).
Lambrecht, B.N. & Hammad, H. Lung dendritic cells in respiratory viral infection and asthma: from protection to immunopathology. Annu. Rev. Immunol. 30, 243–270 (2012).
Licona-Limón, P., Kim, L.K., Palm, N.W. & Flavell, R.A. TH2, allergy and group 2 innate lymphoid cells. Nat. Immunol. 14, 536–542 (2013).
Spergel, J.M. From atopic dermatitis to asthma: the atopic march. Ann. Allergy Asthma Immunol. 105, 99–106 (2010).
Guerra, S. Asthma and chronic obstructive pulmonary disease. Curr. Opin. Allergy Clin. Immunol. 9, 409–416 (2009).
Quentmeier, H. et al. Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation. Leukemia 15, 1286–1292 (2001).
Reche, P.A. et al. Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J. Immunol. 167, 336–343 (2001).
Sims, J.E. et al. Molecular cloning and biological characterization of a novel murine lymphoid growth factor. J. Exp. Med. 192, 671–680 (2000).
Bell, B.D. et al. The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses. Nat. Immunol. 14, 364–371 (2013).
Ziegler, S.F. & Artis, D. Sensing the outside world: TSLP regulates barrier immunity. Nat. Immunol. 11, 289–293 (2010).
Ziegler, S.F. Thymic stromal lymphopoietin and allergic disease. J. Allergy Clin. Immunol. 130, 845–852 (2012).
Ziegler, S.F. et al. The biology of thymic stromal lymphopoietin (TSLP). Adv. Pharmacol. 66, 129–155 (2013).
Leyva-Castillo, J.M. et al. Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat. Commun. 4, 2847 (2013).
Pandey, A. et al. Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat. Immunol. 1, 59–64 (2000).
Park, L.S. et al. Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J. Exp. Med. 192, 659–670 (2000).
Mackall, C.L., Fry, T.J. & Gress, R.E. Harnessing the biology of IL-7 for therapeutic application. Nat. Rev. Immunol. 11, 330–342 (2011).
Noti, M. et al. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat. Med. 19, 1005–1013 (2013).
Redhu, N.S. & Gounni, A.S. Function and mechanisms of TSLP/TSLPR complex in asthma and COPD. Clin. Exp. Allergy 42, 994–1005 (2012).
Siracusa, M.C., Kim, B.S., Spergel, J.M. & Artis, D. Basophils and allergic inflammation. J. Allergy Clin. Immunol. 132, 789–801 (2013).
Wilson, S.R. et al. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 155, 285–295 (2013).
Siracusa, M.C. et al. Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation. Immunity 39, 1158–1170 (2013).
Roan, F. et al. The multiple facets of thymic stromal lymphopoietin (TSLP) during allergic inflammation and beyond. J. Leukoc. Biol. 91, 877–886 (2012).
Datta, A. et al. Evidence for a functional thymic stromal lymphopoietin signaling axis in fibrotic lung disease. J. Immunol. 191, 4867–4879 (2013).
De Monte, L. et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med. 208, 469–478 (2011).
Pedroza-Gonzalez, A. et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J. Exp. Med. 208, 479–490 (2011).
Perez-Andreu, V. et al. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nat. Genet. 45, 1494–1498 (2013).
Hunninghake, G.M. et al. TSLP polymorphisms are associated with asthma in a sex-specific fashion. Allergy 65, 1566–1575 (2010).
Liu, W. et al. Two single nucleotide polymorphisms in TSLP gene are associated with asthma susceptibility in Chinese Han population. Exp. Lung Res. 38, 375–382 (2012).
Torgerson, D.G. et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat. Genet. 43, 887–892 (2011).
Rothenberg, M.E. et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat. Genet. 42, 289–291 (2010).
Borowski, A. et al. Expression analysis and specific blockade of the receptor for human thymic stromal lymphopoietin (TSLP) by novel antibodies to the human TSLPRalpha receptor chain. Cytokine 61, 546–555 (2013).
Romeo, M.J., Agrawal, R., Pomes, A. & Woodfolk, J.A. A molecular perspective on T2-promoting cytokine receptors in patients with allergic disease. J. Allergy Clin. Immunol. (28 September 2013).
Zhang, F., Huang, G., Hu, B., Song, Y. & Shi, Y. A soluble thymic stromal lymphopoietin (TSLP) antagonist, TSLPR-immunoglobulin, reduces the severity of allergic disease by regulating pulmonary dendritic cells. Clin. Exp. Immunol. 164, 256–264 (2011).
Cheng, D.T. et al. Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma. J. Allergy Clin. Immunol. 132, 455–462 (2013).
Kabata, H. et al. Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat. Commun. 4, 2675 (2013).
Walsh, S.T. Structural insights into the common gamma-chain family of cytokines and receptors from the interleukin-7 pathway. Immunol. Rev. 250, 303–316 (2012).
Verstraete, K. et al. Efficient production of bioactive recombinant human Flt3 ligand in E. coli. Protein J. 28, 57–65 (2009).
McCoy, A.J. Solving structures of protein complexes by molecular replacement with Phaser. Acta Crystallogr. D Biol. Crystallogr. 63, 32–41 (2007).
McElroy, C.A., Dohm, J.A. & Walsh, S.T. Structural and biophysical studies of the human IL-7/IL-7Ralpha complex. Structure 17, 54–65 (2009).
Levin, A.M. et al. Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'. Nature 484, 529–533 (2012).
Bondensgaard, K. et al. The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue. J. Biol. Chem. 282, 23326–23336 (2007).
Wang, X., Lupardus, P., Laporte, S.L. & Garcia, K.C. Structural biology of shared cytokine receptors. Annu. Rev. Immunol. 27, 29–60 (2009).
Fass, D. Disulfide bonding in protein biophysics. Annu. Rev. Biophys. 41, 63–79 (2012).
Fry, T.J. & Mackall, C.L. Interleukin-7: from bench to clinic. Blood 99, 3892–3904 (2002).
Vaday, G.G. & Lider, O. Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation. J. Leukoc. Biol. 67, 149–159 (2000).
Cooley, R.B., Arp, D.J. & Karplus, P.A. Evolutionary origin of a secondary structure: pi-helices as cryptic but widespread insertional variations of alpha-helices that enhance protein functionality. J. Mol. Biol. 404, 232–246 (2010).
LaPorte, S.L. et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell 132, 259–272 (2008).
Ring, A.M. et al. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat. Immunol. 13, 1187–1195 (2012).
Shochat, C. et al. Gain-of-function mutations in interleukin-7 receptor-alpha (IL7R) in childhood acute lymphoblastic leukemias. J. Exp. Med. 208, 901–908 (2011).
Zenatti, P.P. et al. Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nat. Genet. 43, 932–939 (2011).
Bernat, B., Pal, G., Sun, M. & Kossiakoff, A.A. Determination of the energetics governing the regulatory step in growth hormone-induced receptor homodimerization. Proc. Natl. Acad. Sci. USA 100, 952–957 (2003).
Verstraete, K. & Savvides, S.N. Extracellular assembly and activation principles of oncogenic class III receptor tyrosine kinases. Nat. Rev. Cancer 12, 753–766 (2012).
Hage, T., Sebald, W. & Reinemer, P. Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface. Cell 97, 271–281 (1999).
Yoda, A. et al. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. USA 107, 252–257 (2010).
Senes, A. et al. E z, a depth-dependent potential for assessing the energies of insertion of amino acid side-chains into membranes: derivation and applications to determining the orientation of transmembrane and interfacial helices. J. Mol. Biol. 366, 436–448 (2007).
White, S.H. & Wimley, W.C. Membrane protein folding and stability: physical principles. Annu. Rev. Biophys. Biomol. Struct. 28, 319–365 (1999).
McElroy, C.A. et al. Structural reorganization of the interleukin-7 signaling complex. Proc. Natl. Acad. Sci. USA 109, 2503–2508 (2012).
Wang, X., Rickert, M. & Garcia, K.C. Structure of the quaternary complex of interleukin-2 with its α, β, and χc receptors. Science 310, 1159–1163 (2005).
Aricescu, A.R., Lu, W. & Jones, E.Y. A time- and cost-efficient system for high-level protein production in mammalian cells. Acta Crystallogr. D Biol. Crystallogr. 62, 1243–1250 (2006).
Reeves, P.J., Callewaert, N., Contreras, R. & Khorana, H.G. Structure and function in rhodopsin: high-level expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracycline-inducible N-acetylglucosaminyltransferase I-negative HEK293S stable mammalian cell line. Proc. Natl. Acad. Sci. USA 99, 13419–13424 (2002).
Verstraete, K. et al. Inducible production of recombinant human Flt3 ectodomain variants in mammalian cells and preliminary crystallographic analysis of Flt3 ligand-receptor complexes. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 67, 325–331 (2011).
Lindner, P. et al. Specific detection of his-tagged proteins with recombinant anti-His tag scFv-phosphatase or scFv-phage fusions. Biotechniques 22, 140–149 (1997).
Kabsch, W. XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010).
Emsley, P., Lohkamp, B., Scott, W.G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010).
Yang, Z. et al. UCSF Chimera, MODELLER, and IMP: an integrated modeling system. J. Struct. Biol. 179, 269–278 (2012).
Larkin, M.A. et al. Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947–2948 (2007).
Gouet, P., Courcelle, E., Stuart, D.I. & Metoz, F. ESPript: analysis of multiple sequence alignments in PostScript. Bioinformatics 15, 305–308 (1999).
Krissinel, E. & Henrick, K. Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr. D Biol. Crystallogr. 60, 2256–2268 (2004).
Word, J.M. et al. Visualizing and quantifying molecular goodness-of-fit: small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol. 285, 1711–1733 (1999).
Dundas, J. et al. CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucleic Acids Res. 34, W116–W118 (2006).
DeLano, W.L. & Lam, J.W. PyMOL: A communications tool for computational models. Abstr. Pap. Am. Chem. Soc. 230, U1371–U1372 (2005).
Howarth, M. & Ting, A.Y. Imaging proteins in live mammalian cells with biotin ligase and monovalent streptavidin. Nat. Protoc. 3, 534–545 (2008).
Pronk, S. et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29, 845–854 (2013).
Lindorff-Larsen, K. et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 78, 1950–1958 (2010).
Eswar, N., Eramian, D., Webb, B., Shen, M.Y. & Sali, A. Protein structure modeling with MODELLER. Methods Mol. Biol. 426, 145–159 (2008).
Zabeau, L. et al. Leptin receptor activation depends on critical cysteine residues in its fibronectin type III subdomains. J. Biol. Chem. 280, 22632–22640 (2005).
Peelman, F. et al. Mapping of the leptin binding sites and design of a leptin antagonist. J. Biol. Chem. 279, 41038–41046 (2004).
Acknowledgements
We thank the staff of beamlines P13 (PetraIII, Deutsches Elektronen-Synchrotron) and Proxima 2A (SOLEIL) for their technical support and beamtime allocation; R. Loris for access to a MicroCal iTC-200 instrument; A. Garcia-Pino and S. De Gieter for assistance during ITC measurements; B. Vekemans and G. Vandriessche for X-ray fluorescence and mass spectrometry measurements, respectively, to confirm the presence of calcium ions and PEG 4000 in crystal form 1A. Supercomputing resources (Stevin Supercomputer Infrastructure) and services were provided by Ghent University, the Hercules Foundation (Belgium) and the Flemish government, department Economie, Wetenschap & Innovatie (EWI). K.V. is supported as postdoctoral fellow by Research Foundation Flanders, Belgium (FWO). Y.B. and L.V. are supported as predoctoral fellows of the Agentschap voor Innovatie door Wetenschap en Technologie (IWT). This work was supported by grants from the FWO (no. G0C2214N to S.N.S. and F.P.), the Hercules Foundation (no. AUGE-11-029 to S.N.S.) and Ghent University (Methusalem grant to J.T.).
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K.V. designed the strategy for recombinant protein production and crystallization. K.V. and L.v.S. created expression constructs, performed protein expression and purification and performed crystallization experiments. K.V. determined and analyzed crystallographic structures with contributions from L.v.S. and S.N.S. K.V. and L.v.S. performed ITC and SPR binding studies. Y.B. performed MALS experiments. K.V., F.P. and S.N.S. designed site-directed mutants and L.V. carried out site-directed mutagenesis. F.P. designed, performed and optimized cellular binding and activity assays with contributions from J.T. E.P. carried out molecular dynamics simulations. K.V. and S.N.S. wrote the manuscript with contributions from all authors. S.N.S. conceived and supervised the project.
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Supplementary Figure 1 Isolation and crystallization of glycan-minimized ternary TSLP–TSLPR– IL-7Rα complexes.
(a) SEC elution profiles of binary TSLPN123Q–TSLPRN122Q complex expressed in HEK293S MGAT1–/– (blue profile) and ternary TSLPN123Q–TSLPRN122Q–IL-7Rα complex (grey profile). Elution volumes of protein standards are indicated above the chromatograms. The Coomassie-stained SDS-PAGE gel shows the binary complex before and after EndoH-treatment, and the resulting ternary complex used to obtain crystal forms 1A and 1B. The molecular masses calculated from the amino acid sequences (i.e. without glycosylation) for recombinant mouse TSLP, TSLPR and IL-7Rα are 15 kDa, 23 kDa and 27 kDa respectively. The TSLPN123Q–TSLPRN53Q–IL-7Rα complex (crystal form 2) was assembled and purified via an identical approach. (b) Cartoon representation of the three structures for the ternary TSLP:TSLPR:IL-7Rα complex determined in this study. Disulfide-bridges are shown as yellow spheres. Potential N-linked glycosylation sites are indicated as blue spheres. The single GlcNAc-residue on TSLPRAsn53 modeled in crystal form 1A is shown as a magenta mesh. (c) Structural superposition of the IL-7RαD2–TSLPRD2 assembly observed in crystal form 2 against the corresponding assembly observed in crystal form 1B.
Supplementary Figure 2 Structure-based sequence comparison between TSLP and IL-7 and evolutionary conserved features in TSLP.
(a) Mature sequences for hTSLP (NP_149024.1), mTSLP (NP_067342.1), mIL-7 (NP_032397.1) and hIL-7 (NP_000871.1) were aligned based on a structural superposition of mTSLP and hIL-7 (pdb 3DI2, chain A) and are annotated according to secondary structure. The 56 residues from which the Cα atoms were included in the structural alignment are highlighted by grey shaded boxes. Dashed lines indicate missing segments in the structural models. Conserved residues are shown in white on a black background. Semi-conserved residues are in black bold and are boxed. Residues in mTSLP and hIL-7 colored blue interact with IL-7Rα, residues of mTSLP colored orange interact with TSLPR. The basic cassette located in the CD-loop of hTSLP is highlighted in red. (b) Structural superposition of mTSLP (blue) and hIL-7 (yellow). mTSLP residues Trp132 and Tyr34, and the corresponding residues in hIL-7, are shown as sticks. (c) View of the evolutionarily conserved hydrophobic core of mTSLP and coordination of the buried water molecule (red sphere), and the internal void volume in the core of TSLP (black mesh). (d) Sequence alignments for sequences of mature TSLP from different mammalian species. mTSLP residues interacting with TSLPR (orange) and IL-7Rα (blue) are indicated. Black lines indicate the conserved disulfide pattern of TSLP. The stretch of basic residues in the CD-loop, present in a subset of TSLP sequences, is highlighted in red. TSLP sequences were derived from the NCBI-database: M. musculus: NP_067342.1, H. sapiens: NP_149024.1, R. norvegicus: XP_001067649.1, M. mulatta: XP_001100503.1, F. catus: XP_003981290.1, O. garnettii: XP_003788993.1, E. caballus: NP_001157535.1, A. melanoleuca: XP_002919224.1
Supplementary Figure 3 Cross-species sequence alignments for the TSLPR ectodomain.
The secondary structure elements correspond to mTSLPR. Dashed lines indicate that the corresponding region was missing in the structural model. Strands are labeled A1-G1 for TSLPRD1 and A2-G2 for TSLPRD2. Conserved residues are shown as white letters on a black background. Semi-conserved residues are shown in black bold and are boxed. mTSLPR residues colored blue interact with mTSLP. Black lines indicate the disulfide pattern of mTSLPR. The atypical PSXW(S/T) motif in TSLPRD2 is indicated by a red box. The predicted transmembrane (TM)-region is shaded blue. Sequences were derived from the NCBI-database: M. musculus: NP_057924.3, H. sapiens: NP_071431.2, R. norvegicus: NP_604460.2, S. scrofa: XP_003361089.1, S. simum: XP_004440836.1, O. aries: XP_004022563.1, O. rosmarus: XP_004400052.1, C. lupus: XP_005641109.1.
Supplementary Figure 4 Cross-species sequence alignments for the IL-7Rα ectodomain.
The secondary structure elements correspond to mIL-7Rα. Dashed lines indicate that the corresponding region was missing in the structural model. Strands are labeled A1-G1 for IL-7RαD1 and A2-G2 for IL-7RαD2. Conserved residues are shown as white letters on a black background. Semi-conserved residues are black bold and are boxed. mIL-7Rα residues colored blue interact with mTSLP, hIL-7Rα residues that interact with hIL-7 are colored orange. Positions that interact with both TSLP and IL-7 are indicated by red dots. Black lines indicate the disulfide bridge network in IL-7Rα. The WSXWS motif in IL-7RαD2 is indicated by a red box. The predicted transmembrane (TM)-region is shaded blue. Sequences were derived from the NCBI-database: M. musculus: NP_032398.3, H. sapiens: NP_002176.2, F. catus: XP_003981510.1, L. africana: XP_003408018.1, C. lupus: XP_855408.1, B. taurus: NP_001192816.1, O. aries: XP_004017102.1, M. domestica: XP_001373020.1 and G. gallus: NP_001073575.1.
Supplementary Figure 5 Biophysical studies to dissect the assembly of TSLP complexes and cellular activity assays to probe observed receptor-receptor contacts at site III.
(a) Coomassie-stained SDS-PAGE gel illustrating the purity of the samples for glycosylated TSLP, TSLPR, IL-7Rα and binary TSLP–TSLPR complex used in the binding studies. (b) ITC thermogram for the titration of 4 mM mIL-7Rα with 46 μM mTSLP. (c-d) Recovered ITC-samples from the titration of TSLP with TSLPR (c) and the titration of IL-7Rα with TSLP–TSLPR (d) were analyzed by MALS. (e) Single-cycle kinetics SPR data for the binding of TSLPR to immobilized TSLP. (f) Cellular activity assays employing TSLPR and IL-7Rα mutants to probe receptor-receptor contacts in site III. TSLP-induced STAT5 activity was measured using a luciferace-based reporter system in HEK293T cells expressing wild type and/or mutant forms of either TSLPR or IL-7Rα upon incubation with wild type TSLP. The determined half-maximum effective concentration (EC50) values for STAT5-activation assays were determined as follows: Control experiment with wild type TSLPR and IL-7Rα (EC50= 0.27 nM); IL-7RαH185A (EC50= 0.31 nM); TSLPRQ162A (EC50= 0.28 nM), TSLPRR180S (EC50= 0.38 nM), and TSLPRD177S (EC50= 0.39 nM). Each experiment was carried out in triplicate and error bars were calculated as s.e.m.
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Verstraete, K., van Schie, L., Vyncke, L. et al. Structural basis of the proinflammatory signaling complex mediated by TSLP. Nat Struct Mol Biol 21, 375–382 (2014). https://doi.org/10.1038/nsmb.2794
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DOI: https://doi.org/10.1038/nsmb.2794
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