The Intrinsic Pepsin Resistance of Interleukin-8 Can Be Explained from a Combined Bioinformatical and Experimental Approach

IEEE/ACM Trans Comput Biol Bioinform. Jan-Feb 2018;15(1):300-308. doi: 10.1109/TCBB.2016.2614821. Epub 2016 Oct 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology / methods*
  • Computer Simulation
  • Interleukin-8 / chemistry*
  • Interleukin-8 / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Pepsin A / chemistry*
  • Pepsin A / metabolism*
  • Protein Binding
  • Protein Structure, Secondary


  • Interleukin-8
  • Pepsin A