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Photo Marie Skepö

Marie Skepö

Professor

Photo Marie Skepö

Interaction of a Histidine-Rich Antimicrobial Saliva Peptide with Model Cell Membranes : The Role of Histidines

Author

  • Amanda Eriksson Skog
  • Giacomo Corucci
  • Mark D Tully
  • Giovanna Fragneto
  • Yuri Gerelli
  • Marie Skepö

Summary, in English

Histatin 5 is a histidine-rich, intrinsically disordered, multifunctional saliva protein known to act as a first line of defense against oral candidiasis caused by Candida albicans. An earlier study showed that, upon interaction with a common model bilayer, a protein cushion spontaneously forms underneath the bilayer. Our hypothesis is that this effect is of electrostatic origin and that the observed behavior is due to proton charge fluctuations of the histidines, promoting attractive electrostatic interactions between the positively charged proteins and the anionic surfaces, with concomitant counterion release. Here we are investigating the role of the histidines in more detail by defining a library of variants of the peptide, where the former have been replaced by the pH-insensitive amino acid glutamine. By using experimental techniques such as circular dichroism, small angle X-ray scattering, quartz crystal microbalance with dissipation monitoring, and neutron reflectometry, it was determined that changing the number of histidines in the peptide sequence did not affect the structure of the peptide dissolved in solution. However, it was shown to affect the penetration depth of the peptide into the bilayer, where all variants except the one with zero histidines were found below the bilayer. A decrease in the number of histidine from the original seven to zero decreases the ability of the peptide to penetrate the bilayer, and the peptide is then also found residing within the bilayer. We hypothesize that this is due to the ability of the histidines to charge titrate, which charges up the peptide, and enables it to penetrate and translocate through the lipid bilayer.

Department/s

  • Department of Chemistry
  • Lund University Bioimaging Center
  • LINXS - Institute of advanced Neutron and X-ray Science
  • Computational Chemistry

Publishing year

2023-06-06

Language

English

Pages

7694-7706

Publication/Series

Langmuir : the ACS journal of surfaces and colloids

Volume

39

Issue

22

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Biophysics

Keywords

  • Histidine
  • Antimicrobial Peptides
  • Saliva/metabolism
  • Lipid Bilayers/chemistry
  • Peptides
  • Cell Membrane/metabolism
  • Anti-Infective Agents/pharmacology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0743-7463