Anders, Gerd, Hassiepen, Ulrich, Theisgen, Stephan, Heymann, Stephan, Muller, Lionel, Panigada, Tania, Huster, Daniel and Samsonov, Sergey (2016) The Intrinsic Pepsin Resistance of Interleukin-8 Can be Explained from a Combined Bioinformatical and Experimental Approach. IEEE TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS, PP (99). p. 1. ISSN 1545-5963

Abstract

Interleukin-8 (IL-8, CXCL8) is a neutrophil chemotactic factor belonging to the family of chemokines. IL-8 was shown to resist pepsin cleavage displaying its high resistance to this protease. However, the molecular mechanisms underlying this resistance are not fully understood. Using our in-house database containing the data on three-dimensional arrangements of secondary structure elements from the whole Protein Data Bank, we found a striking structural similarity between IL-8 and pepsin inhibitor-3. Such similarity could play a key role in understanding IL-8 resistance to the protease pepsin. To support this hypothesis, we applied pepsin assays confirming that intact IL-8 is not degraded by pepsin in comparison to IL-8 in a denaturated state. Applying 1H-15N Heteronuclear Single Quantum Coherence NMR measurements, we determined the putative regions at IL-8 that are potentially responsible for interactions with the pepsin. The results obtained in this work contribute to the understanding of the resistance of IL-8 to pepsin proteolysis in terms of its structural properties.

Item Type:	Article
Keywords:	Immune system, Proteins, Databases, Electronic mail, Three-dimensional displays, Fluorescence, Bioinformatics, interleukin-8, Protein-protein interactions, computational biology, pepsin resistance, pepsin inhibitor
Date Deposited:	09 Nov 2016 00:45
Last Modified:	09 Nov 2016 00:45
URI:	https://oak.novartis.com/id/eprint/29106