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Open data
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Basic information
Entry | Database: SASBDB / ID: SASDB99 |
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![]() | Extracellular assembly of the human TSLP:TSLPR:IL-7Ralpha complex
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Function / homology | ![]() positive regulation of chemokine (C-C motif) ligand 1 production / positive regulation of granulocyte colony-stimulating factor production / interleukin-7 receptor activity / interleukin-7 receptor binding / interleukin-7-mediated signaling pathway / positive regulation of mast cell activation / positive regulation of receptor signaling pathway via STAT / negative regulation of T cell mediated cytotoxicity / regulation of DNA recombination / positive regulation of cytokine-mediated signaling pathway ...positive regulation of chemokine (C-C motif) ligand 1 production / positive regulation of granulocyte colony-stimulating factor production / interleukin-7 receptor activity / interleukin-7 receptor binding / interleukin-7-mediated signaling pathway / positive regulation of mast cell activation / positive regulation of receptor signaling pathway via STAT / negative regulation of T cell mediated cytotoxicity / regulation of DNA recombination / positive regulation of cytokine-mediated signaling pathway / positive regulation of T cell differentiation in thymus / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / negative regulation of T cell apoptotic process / cellular homeostasis / cytokine receptor activity / regulation of cell size / B cell proliferation / T cell homeostasis / cytokine binding / cell surface receptor signaling pathway via JAK-STAT / B cell homeostasis / positive regulation of interleukin-10 production / hemopoiesis / defense response to fungus / lymph node development / positive regulation of chemokine production / positive regulation of tyrosine phosphorylation of STAT protein / Interleukin-7 signaling / clathrin-coated endocytic vesicle membrane / cytokine activity / antigen binding / positive regulation of receptor signaling pathway via JAK-STAT / cell morphogenesis / T cell mediated cytotoxicity / cytokine-mediated signaling pathway / positive regulation of inflammatory response / positive regulation of interleukin-6 production / Cargo recognition for clathrin-mediated endocytosis / antimicrobial humoral immune response mediated by antimicrobial peptide / Clathrin-mediated endocytosis / gene expression / T cell differentiation in thymus / defense response to Gram-negative bacterium / receptor complex / cell surface receptor signaling pathway / defense response to Gram-positive bacterium / immune response / external side of plasma membrane / positive regulation of cell population proliferation / positive regulation of gene expression / negative regulation of apoptotic process / signal transduction / extracellular space / extracellular region / nucleoplasm / plasma membrane / cytosol Similarity search - Function |
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![]() | ![]() Title: Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma. Authors: Kenneth Verstraete / Frank Peelman / Harald Braun / Juan Lopez / Dries Van Rompaey / Ann Dansercoer / Isabel Vandenberghe / Kris Pauwels / Jan Tavernier / Bart N Lambrecht / Hamida Hammad / ...Authors: Kenneth Verstraete / Frank Peelman / Harald Braun / Juan Lopez / Dries Van Rompaey / Ann Dansercoer / Isabel Vandenberghe / Kris Pauwels / Jan Tavernier / Bart N Lambrecht / Hamida Hammad / Hans De Winter / Rudi Beyaert / Guy Lippens / Savvas N Savvides / ![]() ![]() ![]() Abstract: The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is pivotal to the pathophysiology of widespread allergic diseases mediated by type 2 helper T cell (Th2) responses, including asthma ...The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is pivotal to the pathophysiology of widespread allergic diseases mediated by type 2 helper T cell (Th2) responses, including asthma and atopic dermatitis. The emergence of human TSLP as a clinical target against asthma calls for maximally harnessing its therapeutic potential via structural and mechanistic considerations. Here we employ an integrative experimental approach focusing on productive and antagonized TSLP complexes and free cytokine. We reveal how cognate receptor TSLPR allosterically activates TSLP to potentiate the recruitment of the shared interleukin 7 receptor α-chain (IL-7Rα) by leveraging the flexibility, conformational heterogeneity and electrostatics of the cytokine. We further show that the monoclonal antibody Tezepelumab partly exploits these principles to neutralize TSLP activity. Finally, we introduce a fusion protein comprising a tandem of the TSLPR and IL-7Rα extracellular domains, which harnesses the mechanistic intricacies of the TSLP-driven receptor complex to manifest high antagonistic potency. |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
-Data source
SASBDB page | ![]() |
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-Related structure data
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External links
Related items in Molecule of the Month |
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-Models
Model #1113 | ![]() Type: atomic / Software: AllosMod-FoXS (005772e) / Radius of dummy atoms: 1.90 A / Symmetry: P1 / Chi-square value: 5.80855488685 ![]() |
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Sample
![]() | Name: Extracellular assembly of the human TSLP:TSLPR:IL-7Ralpha complex Entity id: 580 / 581 / 582 |
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Buffer | Name: 10 mM Hepes, 150 mM NaCl / pH: 7.4 |
Entity #580 | Name: TSLP / Type: protein / Description: Thymic stromal lymphopoietin / Formula weight: 14.618 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q969D9 Sequence: GSHMYDFTNC DFEKIKAAYL STISKDLITY MSGTKSTEFN NTVSCSNRPH CLTEIQSLTF NPTAGCASLA KEMFAMKTKA ALAIWCPGYS ETQINATQAM KKVTTNKCLE QVSQLQGLWR RFNRPLLKQQ |
Entity #581 | Name: IL-7Rα / Type: protein / Description: Interleukin-7 receptor subunit alpha / Formula weight: 25.672 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P16871 Sequence: GSHMESGYAQ NGDLEDAELD DYSFSCYSQL EVNGSQHSLT CAFEDPDVNI TNLEFEICGA LVEVKCLNFR KLQEIYFIET KKFLLIGKSN ICVKVGEKSL TCKKIDLTTI VKPEAPFDLS VVYREGANDF VVTFNTSHLQ KKYVKVLMHD VAYRQEKDEN KWTHVNLSST ...Sequence: GSHMESGYAQ NGDLEDAELD DYSFSCYSQL EVNGSQHSLT CAFEDPDVNI TNLEFEICGA LVEVKCLNFR KLQEIYFIET KKFLLIGKSN ICVKVGEKSL TCKKIDLTTI VKPEAPFDLS VVYREGANDF VVTFNTSHLQ KKYVKVLMHD VAYRQEKDEN KWTHVNLSST KLTLLQRKLQ PAAMYEIKVR SIPDHYFKGF WSEWSPSYYF RTPEINNSSG EMD |
Entity #582 | Name: TSLPR / Type: protein / Description: Cytokine receptor-like factor 2 / Formula weight: 24.059 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q9HC73 Sequence: GAAEGVQIQI IYFNLETVQV TWQASKYSRT NLTFHYRFNG DEAYDQCTNY LLQEGHTSGC LLDAEQRDDI LYFSIRNGTH PVFTASRWMV YYLKPSSPKH VRFSWHQDAV TVTCSDLSYG DLLYEVQYRS PFDTEWQSKQ ENTCQVTIEG LDAEKCYSFW VRVKAMEDVY ...Sequence: GAAEGVQIQI IYFNLETVQV TWQASKYSRT NLTFHYRFNG DEAYDQCTNY LLQEGHTSGC LLDAEQRDDI LYFSIRNGTH PVFTASRWMV YYLKPSSPKH VRFSWHQDAV TVTCSDLSYG DLLYEVQYRS PFDTEWQSKQ ENTCQVTIEG LDAEKCYSFW VRVKAMEDVY GPDTYPSDWS EVTCWQRGEI RDACAETGTK HHHHHH |
-Experimental information
Beam | Instrument name: SOLEIL SWING ![]() ![]() | |||||||||||||||||||||||||||||||||
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Detector | Name: AVIEX / Type: CCD | |||||||||||||||||||||||||||||||||
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Distance distribution function P(R) |
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