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.
Author Karoline Nordsieck - [Universität Leipzig]
Karoline Nordsieck,,
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, Lars Baumann - [Universität Leipzig]
Lars Baumann,,
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, Vera Hintze - [Technische Universität Dresden]
Vera Hintze,,
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, M. Teresa Pisabarro - [Technische Universität Dresden]
M. Teresa Pisabarro,,
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, Matthias Schnabelrauch - [Innovent e.V.]
Matthias Schnabelrauch,,
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, Annette G. Beck-Sickinger - [Universität Leipzig]
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
Vol109
No10
Pages1-12
Publication size in sheets0.55
Article numbere23103
Keywords in Englishchemokine, interleukin-8, modeling glycosaminoglycan binding, protein–glycosaminoglycan interactions, truncated interleukin-8 variants
ASJC Classification2700 General Medicine; 1303 Biochemistry; 1304 Biophysics; 1605 Organic Chemistry; 2502 Biomaterials
DOIDOI:10.1002/bip.23103
Languageen angielski
LicenseRepository; author's final; Uznanie Autorstwa - Na Tych Samych Warunkach (CC-BY-SA); with publication
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Nordsieck_Karoline_The_effect_of_interleukin-8_truncations_on_its_interactions_with_glycosaminoglycans_2018.pdf 1.09 MB
Score (nominal)25
Score sourcejournalList
ScoreMinisterial score = 25.0, 14-02-2020, ArticleFromJournal
Publication indicators WoS Citations = 3; Scopus Citations = 5; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.574; WoS Impact Factor: 2018 = 1.845 (2) - 2018=2.003 (5)
Citation count*5 (2020-02-13)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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