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Functional characterisation of two receptor interaction determinants in human thymic stromal lymphopoietin

  • Iva Marković ORCID logo , Therese Wolfrum , Andreas Wohlmann , Kritan Gautam and Karlheinz Friedrich EMAIL logo
Published/Copyright: October 26, 2021
Biological Chemistry
From the journal Biological Chemistry Volume 403 Issue 2

Abstract

Thymic stromal lymphopoietin (TSLP) is a pro-inflammatory cytokine with important pathological roles in Asthma bronchiale, malignant tumours and other diseases. The heterodimeric human TSLP receptor (hTSLPR) consists of the TSLP-binding subunit (TSLPRα) and the IL-7Rα-subunit. We studied the properties of hTSLP variants with mutations in their bipartite interaction interface towards IL-7Rα. One mutant (T46D/K101D) showed only mild impairment in receptor affinity but a massive reduction in biological activity. To facilitate the future development of hTSLP mutants with drug properties, we have devised a eukaryontic cytokine display assay with activity read-out and intrinsic genotype-phenotype coupling.

Keywords: cellular surface display; cytokine receptor; thymic stromal lymphopoietin; TSLP
Corresponding author: Karlheinz Friedrich, Institute of Biochemistry II, University Hospital Jena, Nonnenplan 2-4, D-07743 Jena, Germany, E-mail:
Present address: Iva Marković, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Unit for Structural Biology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium Present address: Kritan Gautam, ImmunoTools GmbH, Jena, Germany

Funding source: Deutsche Forschungsgemeinschaft

Award Identifier / Grant number: FR 854/8-1

Acknowledgments

We are grateful to Thomas Müller, University of Würzburg for valuable discussions throughout mutant design and to Sebastian Krause, INVIGATE GmbH, for biotinylated hTSLP.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by grant FR 854/8-1 from the Deutsche Forschungsgemeinschaft.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2021-0293).

Received: 2021-06-13
Accepted: 2021-10-14
Published Online: 2021-10-26
Published in Print: 2022-01-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2021-0293
Keywords for this article
cellular surface display; cytokine receptor; thymic stromal lymphopoietin; TSLP

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Signal Transduction in Health and Disease
  3. Signal transduction in health and disease
  4. Arrestin-dependent internalization of rhodopsin-like G protein-coupled receptors
  5. Post-translational lysine ac(et)ylation in health, ageing and disease
  6. The relevance of adhesion G protein-coupled receptors in metabolic functions
  7. The phytochemical plumbagin reciprocally modulates osteoblasts and osteoclasts
  8. Infection, inflammation and thrombosis: a review of potential mechanisms mediating arterial thrombosis associated with influenza and severe acute respiratory syndrome coronavirus 2
  9. Functional characterisation of two receptor interaction determinants in human thymic stromal lymphopoietin
  10. Corrigendum
  11. Corrigendum to: Emerging mechanisms of drug-induced phospholipidosis
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