Structural insights into heme binding to IL-36α proinflammatory cytokine

Wißbrock A, Goradia NB, Kumar A, Paul George AA, Kühl T, Bellstedt P, Ramachandran R, Hoffmann P, Galler K, Popp J, Neugebauer U, Hampel K, Zimmermann B, Adam S, Wiendl M, Krönke G, Hamza I, Heinemann SH, Frey S, Hueber A, Ohlenschläger O, Imhof D (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 9

Pages Range: 16893-

Journal Issue: 1

DOI: 10.1038/s41598-019-53231-0

Abstract

Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.

Authors with CRIS profile

Susanne Adam Department of Medicine 3 – Rheumatology and Immunology Maximilian Wiendl Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Gerhard Krönke Professur für Translationale Immunologie Silke Frey Department of Medicine 3 – Rheumatology and Immunology Axel Hueber Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) BIAFFIN GmbH & Co KG DE Germany (DE) University of Maryland US United States (USA) (US) Friedrich-Schiller-Universität Jena DE Germany (DE) Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut (FLI) DE Germany (DE) Universitätsklinikum Jena DE Germany (DE) Leibniz-Institut für Photonische Technologien e.V. DE Germany (DE)

How to cite

APA:

Wißbrock, A., Goradia, N.B., Kumar, A., Paul George, A.A., Kühl, T., Bellstedt, P.,... Imhof, D. (2019). Structural insights into heme binding to IL-36α proinflammatory cytokine. Scientific Reports, 9(1), 16893-. https://doi.org/10.1038/s41598-019-53231-0

MLA:

Wißbrock, Amelie, et al. "Structural insights into heme binding to IL-36α proinflammatory cytokine." Scientific Reports 9.1 (2019): 16893-.

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