A deamidated interferon-β variant binds to integrin αvβ3.

Autor: Mastrangeli R; Biotech Development Programme, CMC Science & Intelligence, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Via Luigi Einaudi, 11, 00012 Guidonia Montecelio (Roma), Italy., D'amici F; Pharmaceutical & Analytical Development Biotech Products, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Via Luigi Einaudi, 11, 00012 Guidonia Montecelio (Roma), Italy., D'Acunto CW; Pharmaceutical & Analytical Development Biotech Products, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Via Luigi Einaudi, 11, 00012 Guidonia Montecelio (Roma), Italy., Fiumi S; Pharmaceutical & Analytical Development Biotech Products, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Via Luigi Einaudi, 11, 00012 Guidonia Montecelio (Roma), Italy., Rossi M; Pharmaceutical & Analytical Development Biotech Products, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Via Luigi Einaudi, 11, 00012 Guidonia Montecelio (Roma), Italy., Terlizzese M; Pharmaceutical & Analytical Development Biotech Products, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Via Luigi Einaudi, 11, 00012 Guidonia Montecelio (Roma), Italy., Palinsky W; Biotech Development Programme, Merck Biopharma (an affiliate of Merck KGaA, Darmstadt, Germany), Zone Industrielle de l'Ouriettaz, Aubonne 1170, Switzerland., Bierau H; Biotech Development Programme, CMC Science & Intelligence, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Via Luigi Einaudi, 11, 00012 Guidonia Montecelio (Roma), Italy. Electronic address: horst.bierau@merckgroup.com.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2018 Apr; Vol. 104, pp. 38-41. Date of Electronic Publication: 2018 Feb 06.
DOI: 10.1016/j.cyto.2018.01.024
Abstrakt: Human type I interferons are a family of pleiotropic cytokines with antiviral, anti-proliferative and immunomodulatory activities. They signal through the same cell surface receptors IFNAR1 and IFNAR2 yet evoking markedly different physiological effects. One differentiating factor of interferon-beta (IFN-β) from other type I interferons is the presence of theAsn-Gly-Arg (NGR) sequence motif, which, upon deamidation, converts to Asp-Gly-Arg (DGR) and iso-Asp-Gly-Arg (iso-DGR) motifs. In other proteins, the NGR and iso-DGR motifs are reported as CD13- and αvβ3, αvβ5, αvβ6, αvβ8 and α5β1 integrin-binding motifs, respectively. The scope of this study was to perform exploratory surface plasmon resonance (SPR) experiments to assess the binding properties of a deamidated IFN-β variant to integrins. For this purpose, integrin αvβ3 was selected as a reference model within the iso-DGR- integrin binding members. The obtained results show that deamidated IFN-β binds integrin αvβ3 with nanomolar affinity and that the response was dependent on the deamidation extent. Based on these results, it can be expected that deamidated IFN-β also binds to other integrin family members that are able to bind to the iso-DGR binding motif. The novel binding properties could help elucidate specific IFN-β attributes that under physiological conditions may be modulated by the deamidation.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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