The effect of interleukin-8 truncations on its interactions with glycosaminoglycans

Karoline Nordsieck , Lars Baumann , Vera Hintze , M. Teresa Pisabarro , Matthias Schnabelrauch , Annette G. Beck-Sickinger , Sergey Samsonov

Abstract

The chemokine interleukin-8 (IL-8, CXCL8) plays an important role in inflammatory processes and consecutive wound healing. It recruits primarily neutrophils to infection sites and stimulates their degranulation and phagocytosis in effector cells. IL-8 binds glycosaminoglycans (GAGs), a class of complex linear anionic polysaccharides often organized into diversely sulfated micro-domains, that enriches the protein concentration locally and so facilitate the formation of stable concentration gradients. In this study, we applied experimental and computational techniques to investigate the binding of wild type and truncated IL-8 variants to natural and chemically modified GAGs to gain further insight into the IL-8/GAG interaction. Circular dichroism spectroscopy of IL-8 variants did not reveal major structural changes upon GAG binding. Heparin affinity chromatography clearly demonstrates that gradual truncation of the C-terminal helix leads to decreasing affinities. Similarly, surface plasmon resonance indicates participation of both IL-8 termini in GAG binding, which strength is dependent on GAG sulfation degree. Molecular modeling suggests that C-terminal truncation of IL-8 weakens the interaction with GAGs by an alteration of IL-8 GAG binding site. Our study provides more detailed understanding of the IL-8/GAG interaction and contributes to the data of potential use for the development of biomedical implications in tissue regeneration.
Publication typeIn press (online first, early view)
Author Karoline Nordsieck
Karoline Nordsieck,,
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, Lars Baumann
Lars Baumann,,
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, Vera Hintze
Vera Hintze,,
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, M. Teresa Pisabarro
M. Teresa Pisabarro,,
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, Matthias Schnabelrauch
Matthias Schnabelrauch,,
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, Annette G. Beck-Sickinger
Annette G. Beck-Sickinger,,
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, Sergey Samsonov (FCh / DTCh / LMM)
Sergey Samsonov,,
- Laboratory of Molecular Modeling
Journal seriesBiopolymers, ISSN 0006-3525, e-ISSN 1097-0282, (A 25 pkt)
Issue year2018
Pages1-12
Publication size in sheets0.55
Keywords in Englishchemokine, interleukin-8, modeling glycosaminoglycan binding, protein–glycosaminoglycan interactions, truncated interleukin-8 variants
DOIDOI:10.1002/bip.23103
URL https://onlinelibrary.wiley.com/doi/epdf/10.1002/bip.23103
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 10-11-2018, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 10-11-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 1.908 (2) - 2016=2.225 (5)
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